CN103076296A

CN103076296A - Background interference elimination method for UV visible absorption spectrum of optical fiber in situ drug dissolution/releasing rate tester

Info

Publication number: CN103076296A
Application number: CN2010101255438A
Authority: CN
Inventors: 胡旭; 王良玉; 张奇洲; 李华西; 李新霞; 李翔
Original assignee: XINJIANG FUKESI BIOTECHNOLOGY DEVELOPMENT Co Ltd
Current assignee: Shanghai FOCS Analysis Instrument Co., Ltd.
Priority date: 2010-03-16
Filing date: 2010-03-16
Publication date: 2013-05-01
Anticipated expiration: 2030-03-16
Also published as: CN103076296B

Abstract

One purpose of the invention is to disclose a background interference elimination method for a UV visible absorption spectrum. With the method, correction can be carried out on absorbance at any wavelength in a spectrum chart to eliminate background interference so as to obtain a complete UV visible absorption spectrum with eliminated background interference, and errors are minimized in the process of correction; thus, the method is particularly applicable to the field of substance analysis in need for accurate determination, especially to analysis of a dissolution/releasing rate of a drug in the process of dissolution. The background interference elimination method disclosed in the invention is particularly applicable to an optical fiber in situ drug dissolution/releasing rate tester to eliminate background interference brought by other substances in a solution to be tested so as to obtain a real-time concentration curve of a to-be-tested substance, especially to obtain a concentration-time curve of a dissolution/releasing rate of a solid drug preparation (a tablet, a capsule, etc.).

Description

The background interference elimination method of the ultraviolet-visible absorption spectroscopy of a kind of optical fiber in site online drug dissolution/dissolution test instrument

Technical field

The present invention relates to a kind of background interference elimination method of ultraviolet-visible absorption spectroscopy, particularly optical fiber in site online drug dissolution/ultraviolet-visible absorption spectroscopy that the dissolution test instrument obtains is carried out the method for background interference elimination.

Background technology

K ratio method is a kind of quantitative spectrograhic analysis method based on the ultraviolet-visible absorption spectroscopy principle, it is the ultraviolet-visible absorption spectroscopy according to potpourri, calculate the method for certain concentration of component in the potpourri, be used for elimination and measure the interference that the auxiliary material of drug-eluting process causes.

In the process of pharmaceutical solid preparation stripping, be accompanied by the stripping of effective ingredient, also along with together dissolving, therefore, the absorption spectrum that directly obtains by spectra collection in the mensuration process is the absorption spectrum that has comprised the potpourri of medicine to be measured and auxiliary material and other materials to excipient substance.In process is measured, need to eliminate the interference of auxiliary material or other materials, K ratio method is exactly a kind of method of disturbing for eliminating auxiliary material.

Absorption spectrum is the characteristic absorption curve of material (compound), often take wavelength X (nm of unit) as horizontal ordinate, take absorbance log A as ordinate, describes the curve that absorbance log changes with wavelength variations.Lambert-beer's law (Lambert BeerLaw) has been set forth material concentration, the relation of liquid layer thickness and radiation intensity, and its formula is

In the formula, A is absorbance log, and T is transmittance, and E is absorption coefficient, and c is the concentration of solution, and l is liquid layer thickness.According to Lambert-beer's law, can in the situation that the known absorbing degree, obtain the concentration of test substance.

Absorbance log possesses the adduction characteristic.In same solution, when containing two kinds or two or more extinction material (without interacting), the absorbance log of this solution equal this wavelength have absorption each material absorbance log and, the additive properties of absorbance log that Here it is.The additive properties of absorbance log is the basis of K-ratio Spectrophotometry.

Yet in the prior art, by gathering the reflected light in the solution to be measured, adopt again the optical instruments such as spectro-grating to carry out light splitting and obtain spectrum, thereby further obtain the characteristic absorption curve of determinand, namely take wavelength X as horizontal ordinate and the curve take absorbance A as ordinate.Subsequently, according to curve obtained, select unique point (such as crest, reference wavelength place), obtain wavelength X and the absorbance A at this some place, subsequently according to K ratio method, the absorbance A of above-mentioned unique point is proofreaied and correct, eliminate the background interference at this some place.

In the above-mentioned prior art, although can according to the ultraviolet-visible absorption spectroscopy that obtains, to unique point, such as crest, carry out the background interference that Data correction is eliminated this some place.Yet, in this conventional art, be by obtaining patterned spectrum spectrogram, the selected characteristic point, the correction feature point obtains for the data of the characteristic absorption peak of judging the determinand kind.So, this conventional art can only obtain one without the absorbance of the ultraviolet-visible absorption spectroscopy spectrogram of background interference elimination and some isolated unique points, can't obtain through overcorrect, can truly show determinand at the ultraviolet-visible absorption spectroscopy spectrogram of the absorbance at each wavelength place.And, owing to having error the process that reads characteristic point data and reference point data from spectrum spectrogram, the also corresponding error that exists in the trimming process of corresponding background interference elimination, and this error is further amplified in each step correction calculation, so have larger error in the process of available technology adopting K ratio method correction ultraviolet-visible absorption spectroscopy, and this error is needing the species analysis of Accurate Measurement, such as Pharmaceutical Analysis, the particularly dissolution rate of drug-eluting process/release analysis will affect accuracy and the reliability of corresponding analysis greatly.

To sum up, need now a kind of background interference elimination method of ultraviolet-visible absorption spectroscopy, solve the problems referred to above.

Simultaneously, in the process of pharmaceutical solid preparation stripping, be accompanied by the stripping of effective ingredient, excipient substance is also along with together dissolving, therefore, in the real time measure process, the absorption spectrum that directly obtains by spectra collection is the absorption spectrum that has comprised the potpourri of medicine to be measured and auxiliary material and other materials.In real-time process is measured, need the interference of elimination auxiliary material or other materials, therefore need to adopt K ratio method to eliminate auxiliary material interference in the process in leaching.Especially, in order to obtain the accurate ultraviolet-visible absorption spectroscopy of effective ingredient, need to proofread and correct the absorbance at each wavelength place of the absorption spectrum that obtains, eliminating background interference, but not only proofread and correct the absorbance that individual characteristics is pointed out.

Therefore, at the Pharmaceutical Analysis detection field, need now a kind of background interference elimination method of ultraviolet-visible absorption spectroscopy, the auxiliary material of eliminating in the pharmaceutical preparation disturbs, thereby proofreaies and correct the ultraviolet-visible absorption spectroscopy of effective ingredient.

Summary of the invention

One of purpose of the present invention is to disclose a kind of background interference elimination method of ultraviolet-visible absorption spectroscopy, it can proofread and correct to eliminate background interference to the absorbance at arbitrary wavelength place in the spectrum spectrogram, thereby obtain a ultraviolet-visible absorption spectroscopy complete, that eliminate background interference, and in above-mentioned trimming process, with error minimize, thereby so that the method is specially adapted to carry out the dissolution rate in the species analysis field of Accurate Measurement, particularly drug-eluting process/release analysis.

Two of purpose of the present invention is to disclose a kind of background interference elimination method of ultraviolet-visible absorption spectroscopy, it goes for optical fiber in site online drug dissolution/dissolution test instrument, and described dissolution rate/dissolution test instrument is open in applicant's of the present invention Chinese patent application the 200410001756.4th and 200410001179.9.Described background interference elimination method is a kind of data processing method based on chemical analysis method medium ultraviolet visible spectrophotometry, in optical fiber in site online drug dissolution/dissolution test instrument and dissolution rate the real time measure software thereof, in the real time measure dissolution rate process, be used for eliminating other material of solution to be measured to the interference of test substance, obtain the real-time concentration curve of test substance, especially for the concentration time curve that obtains pharmaceutical solid preparation (tablet, capsule etc.) dissolution rate or release.

Optical fiber in site online drug dissolution involved in the present invention/dissolution test instrument comprises digestion instrument, the light source, y-type optical fiber, detection module and the microprocessor module that link to each other successively, described y-type optical fiber connects light source, detection module and digestion instrument simultaneously, and described detection module comprises grating beam splitting module, photodiode array module, signal amplification module and the analog-digital converter that links to each other successively.

Described light source adopts deuterium lamp or xenon lamp or mercury lamp or xenon/mercury lamp or laser instrument.

Described y-type optical fiber is the two branch optical fibers of one or more Y type and sensor probe.The two branch optical fibers of described Y type and sensor probe comprise sleeve pipe, optical fiber and reflective mirror, the test side of optical fiber is installed in the inner end of sleeve pipe, outer end at sleeve pipe is equipped with adjusting light path bar by engage thread or inserted mode, at the inner end of regulating the light path bar reflective mirror is installed, has at the middle part of sleeve pipe to be no less than one injection port.

The inboard of described reflective mirror can be equipped with sensitive membrane.The described reflective mirror outside can be coated with the ultraviolet reflectance film.The test side of described optical fiber can be equipped with the optical fiber focus lamp.Described optical fiber can adopt single mode silica fibre or the multimode silica fibre of Y type.

Described detection module adopts charge-coupled detector(CCD) CCD, cmos image sensor CMOS, electric charge injector CID or diode array DAD detecting device.

The background interference elimination method of described uv-vis spectra comprises following steps:

Step 1: described light source is to the light of y-type optical fiber input wavelength λ scope at 200～1100nm;

Step 2: described y-type optical fiber by with the probe of its end with in the blank solution of described wavelength X scope in the light input digestion instrument of 200～1100nm, adopt subsequently described probe to gather light signal, and the gained light signal is transmitted it to detection module through y-type optical fiber;

The light signal of gained blank solution is inputted grating beam splitting module, photodiode array module, signal amplification module and analog-digital converter successively, export the digital signal of described light signal, obtain the light intensity I at a plurality of one to one different wave length λ place _BlankThereby, generate the light intensity spectral information, and transmit it to microprocessor module;

Step 3: described y-type optical fiber by with the probe of its end with in the mixed solution of wavelength X scope in the light input digestion instrument of 200～1100nm, adopt subsequently probe to gather light signal, and the light signal of gained solution to be measured is transmitted it to detection module through y-type optical fiber;

Contain auxiliary material and determinand in the described mixed solution;

The light signal of gained mixed solution is inputted grating beam splitting module, photodiode array module, signal amplification module and analog-digital converter successively, export the digital signal of described light signal, obtain the light intensity I at a plurality of one to one different wave length λ place _MixThereby, generate the light intensity spectral information, and transmit it to microprocessor module;

Step 4: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, the light intensity spectrum of mixed solution, a plurality of one to one different wave length λ place light intensity I _Mix, adopt formula A in each af at wavelength lambda _Mix=-lg (I _Mix/ I _Blank), calculate mixed solution in the absorbance of each af at wavelength lambda, obtain the absorbance A to be corrected at a plurality of one to one different wave length λ place _MixThereby, obtain the ultraviolet-visible absorption spectroscopy of mixed solution;

Step 5: the ultraviolet-visible absorption spectroscopy that obtains auxiliary material solution;

Step 6: call in the standard ultraviolet-visible absorption spectroscopy of determinand from microprocessor, choose the mensuration wavelength of determinand as the mensuration wavelength X of mixed solution _Measure, perhaps according to the ultraviolet-visible absorption spectroscopy of mixed solution, compare successively the absorbance A of each af at wavelength lambda _Mix, determine maximum absorbance A _MaxCorresponding wavelength is chosen it as measuring wavelength X _Measure

Step 7: call in the standard ultraviolet-visible absorption spectroscopy of determinand and the ultraviolet-visible absorption spectroscopy of gained auxiliary material solution from microprocessor, select reference wavelength λ _Reference, described reference wavelength λ _ReferenceThe place, the absorbance A of the standard ultraviolet-visible absorption spectroscopy of determinand is less than 0.01, and the absorbance A of the ultraviolet-visible absorption spectroscopy of auxiliary material solution is greater than 0.01;

Step 8: according to the ultraviolet-visible absorption spectroscopy of gained auxiliary material solution, obtain auxiliary material solution and measuring wavelength X _MeasureWith reference wavelength λ _ReferenceThe absorbance A at place _Measure' and A _Reference';

According to formula k=A _Measure'/A _Reference', obtain K-ratio k;

Step 9: according to the ultraviolet-visible absorption spectroscopy of gained mixed solution, obtain mixed solution and measuring wavelength X _MeasureWith reference wavelength λ _ReferenceThe absorbance A at place _Measure" and A _Reference";

Step 10: according to formula A _Measure=A _Measure"-kA _Reference", the mixed solution that obtains containing determinand and auxiliary material is after the interference of eliminating auxiliary material, and determinand is wherein being measured wavelength X _MeasureThe absorbance A at place _Measure

In a preferred embodiment, described step 2 is further comprising the steps:

Step 2.1: described y-type optical fiber by with the probe of its end with in the blank solution of described wavelength X scope in the light input digestion instrument of 200～1100nm, adopt subsequently described probe to gather light signal, and the gained light signal is transmitted it to detection module through y-type optical fiber;

Step 2.2: optical signal transmission to the grating beam splitting module of gained blank solution is carried out light splitting, obtain spectrum;

Step 2.3: the gained spectral transmissions to the photodiode array module, is converted into corresponding electric signal with light signal, obtains the light intensity I of the light at different wave length λ place _BlankElectric signal;

Step 2.4: resulting electric signal transmission to signal amplification module is amplified, transfer to subsequently analog-digital converter, electric signal is converted into corresponding digital signal, obtain the light intensity I of the light at different wave length λ place _BlankDigital signal;

Step 2.5: with the gained digital data transmission to microprocessor module, subsequently according to gained one to one wavelength X and light intensity I _BlankData, generate the light intensity spectrum of blank solution.

In a preferred embodiment, described step 3 is further comprising the steps:

Step 3.1: described y-type optical fiber by with the probe of its end with in the mixed solution of described wavelength X scope in the light input digestion instrument of 200～1100nm, adopt subsequently described probe to gather light signal, and the gained light signal is transmitted it to detection module through y-type optical fiber;

Step 3.2: optical signal transmission to the grating beam splitting module of gained mixed solution is carried out light splitting, obtain spectrum;

Step 3.3: the gained spectral transmissions to the photodiode array module, is converted into corresponding electric signal with light signal, obtains the light intensity I of the light at different wave length λ place _MixElectric signal;

Step 3.4: resulting electric signal transmission to signal amplification module is amplified, transfer to subsequently analog-digital converter, electric signal is converted into corresponding digital signal, obtain the light intensity I of the light at different wave length λ place _MixDigital signal;

Step 3.5: with the gained digital data transmission to microprocessor module, subsequently according to gained one to one wavelength X and light intensity I _MixData, generate the light intensity spectrum of mixed solution.

The ultraviolet-visible absorption spectroscopy of the auxiliary material solution in the described step 5 can obtain by 4 kinds of methods:

1, calls in the standard ultraviolet-visible absorption spectroscopy of auxiliary material from microprocessor, as the spectrum in the actual measurement process;

2, configuration auxiliary material solution is measured the light intensity spectrum of auxiliary material solution, and then generates ultraviolet-visible absorption spectroscopy;

3, in the situation that auxiliary material is difficult to obtain or auxiliary material not clear, call in the standard ultraviolet-visible absorption spectroscopy of determinand from microprocessor, the ultraviolet-visible absorption spectroscopy of the good after measured determinand standard ultraviolet-visible absorption spectroscopy with the determinand of calling in is subtracted each other, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material;

4, in the situation that auxiliary material is difficult to obtain or auxiliary material not clear, the standard solution of configuration determinand, measure the light intensity spectrum of the standard solution of determinand, and then the ultraviolet-visible absorption spectroscopy of the standard solution of generation determinand, the ultraviolet-visible absorption spectroscopy of the standard solution of the ultraviolet-visible absorption spectroscopy of good after measured determinand and determinand is subtracted each other, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material.

In a preferred embodiment, adopt first method.Therefore in the described step 5, call in the standard ultraviolet-visible absorption spectroscopy of auxiliary material from microprocessor, as the ultraviolet-visible absorption spectroscopy of described auxiliary material solution, thereby obtain the absorbance A at a plurality of one to one different wave length λ place of auxiliary material solution _{Auxiliary material}

In a preferred embodiment, adopt second method.Described step 5 is further comprising the steps:

Step 5.1: described y-type optical fiber by with the probe of its end with in the auxiliary material solution of described wavelength X scope in the light input digestion instrument of 200～1100nm, adopt subsequently described probe to gather light signal, and the gained light signal is transmitted it to detection module through y-type optical fiber;

Step 5.2: optical signal transmission to the grating beam splitting module of gained auxiliary material solution is carried out light splitting, obtain spectrum;

Step 5.3: the gained spectral transmissions to the photodiode array module, is converted into corresponding electric signal with light signal, obtains the light intensity I of the light at different wave length λ place _{Auxiliary material}Electric signal;

Step 5.4: resulting electric signal transmission to signal amplification module is amplified, transfer to subsequently analog-digital converter, electric signal is converted into corresponding digital signal, obtain the light intensity I of the light at different wave length λ place _{Auxiliary material}Digital signal;

Step 5.5: with the gained digital data transmission to microprocessor module, subsequently according to gained one to one wavelength X and light intensity I _{Auxiliary material}Data, generate the light intensity spectrum of auxiliary material solution;

Step 5.6: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, the light intensity spectrum of auxiliary material solution, a plurality of one to one different wave length λ place light intensity I _{Auxiliary material}, adopt formula A in each af at wavelength lambda _{Auxiliary material}=-lg (I _{Auxiliary material}/ I _Blank), calculate auxiliary material solution in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Auxiliary material}Thereby, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

In a preferred embodiment, adopt the third method.Described step 5 is further comprising the steps:

Step 5.1: call in the standard ultraviolet-visible absorption spectroscopy of determinand from microprocessor, obtain the standard absorbance A at a plurality of one to one different wave length λ place of determinand _{Standard is to be measured}

Step 5.2: according to the absorbance A to be corrected at a plurality of one to one different wave length λ place of gained mixed solution in the step 4 _Mix, the standard absorbance A at a plurality of one to one different wave length λ place of step 5.1 gained determinand _{Standard survey to be measured}, according to formula A _{Auxiliary material}=A _Mix-A _{Standard is to be measured}, calculate auxiliary material solution in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Auxiliary material}Thereby, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

In a preferred embodiment, adopt the 4th kind of method.Described step 5 is further comprising the steps:

Step 5.1: the standard solution of configuration determinand;

Step 5.2: described y-type optical fiber is by inputting described wavelength X scope in the standard solution of the determinand in the digestion instrument at the light of 200～1100nm with the probe of its end, adopt subsequently described probe to gather light signal, and the gained light signal is transmitted it to detection module through y-type optical fiber;

Step 5.3: optical signal transmission to the grating beam splitting module of the standard solution of gained determinand is carried out light splitting, obtain spectrum;

Step 5.4: the gained spectral transmissions to the photodiode array module, is converted into corresponding electric signal with light signal, obtains the light intensity I of the light at different wave length λ place _{Standard is to be measured}Electric signal;

Step 5.5: resulting electric signal transmission to signal amplification module is amplified, transfer to subsequently analog-digital converter, electric signal is converted into corresponding digital signal, obtain the light intensity I of the light at different wave length λ place _{Standard is to be measured}Digital signal;

Step 5.6: with the gained digital data transmission to microprocessor module, subsequently according to gained one to one wavelength X and light intensity I _{Auxiliary material}Data, generate the light intensity spectrum of the standard solution of determinand;

Step 5.7: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, determinand the light intensity spectrum, the light intensity I at a plurality of one to one different wave length λ place of standard solution _{Standard is to be measured}, adopt formula A in each af at wavelength lambda _{Standard is to be measured}=-lg (I _{Standard is to be measured}/ I _Blank), calculate the standard solution of determinand in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Standard is to be measured}

Step 5.8: according to the absorbance A to be corrected at a plurality of one to one different wave length λ place of gained mixed solution in the step 4 _Mix, the absorbance A at a plurality of one to one different wave length λ place of the standard solution of step 5.7 gained determinand _{Standard is to be measured}, according to formula A _{Auxiliary material}=A _Mix-A _{Standard is to be measured}, calculate auxiliary material solution in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Auxiliary material}Thereby, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

In a preferred embodiment, described photodiode array module is the photodiode array of m * n, m=1～8 wherein, n 〉=128.Each pixel on the first axle of described photodiode array is labeled as 0 successively, 1...m.Each pixel on the second axle of described photodiode array is labeled as 0,1 successively, 2...n.The second axle of described photodiode array is parallel with described grating beam splitting module.Described photodiode array is converted to corresponding electric signal with the light signal that each diode place accepts, thereby obtains the electric signal of corresponding pixel.

In a preferred embodiment, described photodiode array module is the photodiode array of m * n, m=1 wherein, n=128,256,1024,2048,4096.Along the second axle of described photodiode array, successively the sequence number x of each pixel of mark be 0,1,2...n.

In a preferred embodiment, adopt the photodiode array of m * n, described step 2 is further comprising the steps:

Step 2.3: with the photodiode array module of gained spectral transmissions to m * n, form m * n pixel, the light signal of the light intensity at each pixel place is converted into electric signal, organize one to one pixel sequence number x and light intensity I thereby obtain n _BlankElectric signal, wherein x represents x pixel, x value 0～n, the light wavelength at this pixel place is λ _x, the light intensity at this pixel place is I _{X is blank}

Step 2.4: resulting n is organized one to one pixel sequence number x and light intensity I _BlankElectric signal transmission to signal amplification module amplify, transfer to subsequently analog-digital converter, the electric signal at each pixel place is converted into corresponding digital signal, obtain n and organize one to one pixel sequence number x and light intensity I _BlankDigital signal;

Step 2.5: gained n is organized one to one pixel sequence number x and light intensity I _BlankDigital data transmission to microprocessor module, according to formula λ _x=λ ₀+ C ₁X+C ₂X ²+ C ₃X ³, calculate the light wavelength at each pixel place, obtain n group one to one x pixel and wavelength X _xDigital signal;

Wherein, x is the sequence number of pixel, λ _xBe the light wavelength at this pixel place, λ ₀Be the light wavelength at the 0th pixel place, C ₁, C ₂And C ₃Be the coefficient relevant with pixel resolution;

Step 2.6: organize one to one pixel sequence number x and light intensity I according to n _BlankDigital signal and n group one to one x pixel and wavelength X _xDigital signal, obtain x the corresponding wavelength X in pixel place _xWith light intensity I _{X is blank}Data, and then generate n and organize one to one wavelength X _xWith light intensity I _{X is blank}Data, generate the light intensity spectrum of blank solution.

In a preferred embodiment, adopt the photodiode array of m * n, described step 3 is further comprising the steps:

Step 3.2: optical signal transmission to the grating beam splitting module of gained solution to be measured is carried out light splitting, obtain spectrum;

Step 3.3: with the photodiode array module of gained spectral transmissions to m * n, form m * n pixel, the light signal of the light intensity at each pixel place is converted into electric signal, organize one to one pixel sequence number x and light intensity I thereby obtain n _{To be measured}Electric signal, wherein x represents x pixel, x value 0～n, the light wavelength at this pixel place is λ _x, the light intensity at this pixel place is I _{X is to be measured}

Step 3.4: resulting n is organized one to one pixel sequence number x and light intensity I _{To be measured}Electric signal transmission to signal amplification module amplify, transfer to subsequently analog-digital converter, the electric signal at each pixel place is converted into corresponding digital signal, obtain n and organize one to one pixel sequence number x and light intensity I _{To be measured}Digital signal;

Step 3.5: gained n is organized one to one pixel sequence number x and light intensity I _{To be measured}Digital data transmission to microprocessor module, according to formula λ _x=λ ₀+ C ₁X+C ₂X ²+ C ₃X ³, calculate the light wavelength at each pixel place, obtain n group one to one x pixel and wavelength X _xDigital signal;

Step 3.6: organize one to one pixel sequence number x and light intensity I according to n _{To be measured}Digital signal and n group one to one x pixel and wavelength X _xDigital signal, obtain x the corresponding wavelength X in pixel place _xWith light intensity I _{X is to be measured}Data, and then generate n and organize one to one wavelength X _xWith light intensity I _{X is to be measured}Data, generate the light intensity spectrum of solution to be measured.

In a preferred embodiment, adopt the photodiode array of m * n, in the described step 4, organize one to one wavelength X according to light intensity spectrum, the n of described blank solution _xWith light intensity I _{X is blank}Data, the light intensity spectrum of solution to be measured, n organize one to one wavelength X _xWith light intensity I _{X is to be measured}Data, to the light intensity I of the blank solution at Same Wavelength λ place _BlankLight intensity I with solution to be measured _{To be measured}, employing formula A '=-lg (I _{To be measured}/ I _Blank), calculate mixed solution in the absorbance A of this af at wavelength lambda _Mix

Wherein, wavelength X _xThe absorbance at place is A _{X mixes}Thereby, obtain n and organize one to one wavelength X _xAnd absorbance A _{X mixes}Data, and then obtain the ultraviolet-visible absorption spectroscopy of solution to be measured.

In a preferred embodiment, adopt the photodiode array of m * n, described step 5 is further comprising the steps:

Step 5.3: with the photodiode array module of gained spectral transmissions to m * n, form m * n pixel, the light signal of the light intensity at each pixel place is converted into electric signal, organize one to one pixel sequence number x and light intensity I thereby obtain n _{Auxiliary material}Electric signal, wherein x represents x pixel, x value 0～n, the light wavelength at this pixel place is λ _x, the light intensity at this pixel place is I _{The x auxiliary material}

Step 5.4: resulting n is organized one to one pixel sequence number x and light intensity I _{Auxiliary material}Electric signal transmission to signal amplification module amplify, transfer to subsequently analog-digital converter, the electric signal at each pixel place is converted into corresponding digital signal, obtain n and organize one to one pixel sequence number x and light intensity I _{Auxiliary material}Digital signal;

Step 5.5: gained n is organized one to one pixel sequence number x and light intensity I _{Auxiliary material}Digital data transmission to microprocessor module, according to formula λ _x=λ ₀+ C ₁X+C ₂X ²+ C ₃X ³, calculate the light wavelength at each pixel place, obtain n group one to one x pixel and wavelength X _xDigital signal;

Step 5.6: organize one to one pixel sequence number x and light intensity I according to n _{Auxiliary material}Digital signal and n group one to one x pixel and wavelength X _xDigital signal, obtain x the corresponding wavelength X in pixel place _xWith light intensity I _{The x auxiliary material}Data, and then generate n and organize one to one wavelength X _xWith light intensity I _{The x auxiliary material}Data, generate the light intensity spectrum of solution to be measured;

Step 5.7: light intensity spectrum, n according to described blank solution organize one to one wavelength X _xWith light intensity I _{X is blank}Data, the light intensity spectrum of auxiliary material solution, n organize one to one wavelength X _xWith light intensity I _{The x auxiliary material}Data, to the light intensity I of the blank solution at Same Wavelength λ place _BlankLight intensity I with solution to be measured _{Auxiliary material}, employing formula A '=-lg (I _{Auxiliary material}/ I _Blank), calculate mixed solution in the absorbance A of this af at wavelength lambda _{Auxiliary material}

Wherein, wavelength X _xThe absorbance at place is A _{The x auxiliary material}Thereby, obtain n and organize one to one wavelength X _xAnd absorbance A _{The x auxiliary material}Data, and then obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

In a preferred embodiment, adopt the photodiode array of m * n, adopt the standard ultraviolet-visible absorption spectroscopy of determinand in the described step 6, choose the mensuration wavelength of determinand as the mensuration wavelength X of mixed solution _Measure

In a further advantageous embodiment, adopt the photodiode array of m * n, adopt the ultraviolet-visible absorption spectroscopy of mixed solution to decide wavelength X in the described step 6 _Measure, it is further comprising the steps:

Ultraviolet-visible absorption spectroscopy and n according to solution to be measured organize one to one wavelength X _xAnd absorbance A _{X mixes}Data, wavelength X relatively successively ₁, λ ₂, λ ₃... λ _nLocate corresponding absorbance A _{Mix 1}, A _{Mix 2}, A _{Mix 3}... A _{Mix n}, choosing wherein, maximum absorbance is labeled as A _Max, the corresponding wavelength of this absorbance of mark is for measuring wavelength X _Measure

In a preferred embodiment, adopt the photodiode array of m * n, described step 7 may further comprise the steps:

Step 7.1: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _{The x auxiliary material}Data, from λ ₁, λ ₂, λ ₃... λ _nIn filter out A _{Auxiliary material 1}, A _{Auxiliary material 2}, A _{Auxiliary material 3}... A _{Auxiliary material n}In greater than the corresponding wavelength X of 0.01 absorbance ';

Step 7.2: according to the standard ultraviolet-visible absorption spectroscopy of determinand, judge successively above-mentioned each wavelength X ' the standard absorbance A ' of corresponding determinand, filter out among each standard absorbance A ' less than the corresponding wavelength X of 0.01 absorbance ";

Step 7.3: optional each wavelength X of gained " in one as reference wavelength λ _Reference

In a preferred embodiment, adopt the photodiode array of m * n, described step 8 may further comprise the steps:

Step 8.1: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _{The x auxiliary material}Data, determine λ _MeasureCorresponding absorbance A _Measure';

Step 8.2: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _{The x auxiliary material}Data, determine λ _ReferenceCorresponding absorbance A _Reference';

Step 8.3: according to formula k=A _Measure'/A _Reference', obtain K-ratio k.

In a preferred embodiment, adopt the photodiode array of m * n, described step 9 may further comprise the steps:

Step 9.1: ultraviolet-visible absorption spectroscopy and n according to mixed solution organize one to one wavelength X _xAnd absorbance A _MixData, determine λ _MeasureCorresponding absorbance A _Measure";

Step 9.2: ultraviolet-visible absorption spectroscopy and n according to mixed solution organize one to one wavelength X _xAnd absorbance A _MixData, determine λ _ReferenceCorresponding absorbance A _Reference".

In a preferred embodiment, adopt the photodiode array of m * n, described method further comprises step 11, and described step 11 is further comprising the steps:

Step 11.1: ultraviolet-visible absorption spectroscopy and n according to the gained mixed solution organize one to one wavelength X _xAnd absorbance A _MixData, adopt formula A=A _Mix-kA _Reference", proofread and correct successively each wavelength X ₁, λ ₂, λ ₃... λ _nCorresponding each absorbance A _{Mix 1}, A _{Mix 2}, A _{Mix 3}... A _{Mix n}, the absorbance A after obtaining proofreading and correct ₁, A ₂, A ₃... A _n, the mixed solution that namely obtains containing determinand and auxiliary material is after the interference of eliminating auxiliary material, and determinand wherein is in the absorbance A of each af at wavelength lambda;

Step 11.2: organize one to one wavelength X according to the n after proofreading and correct _xAnd absorbance A _x, generate the ultraviolet-visible absorption spectroscopy of mixed solution after the background interference of eliminating auxiliary material.

According to above-mentioned steps of the present invention, at first gather the light of solution to be measured, adopt subsequently the grating beam splitting module with the light splitting of gained light, obtain spectrum, gained spectrum is projected on the photodiode array of m * n, obtain m * n pixel.The second axle of wherein said photodiode array is parallel with the grating beam splitting module, described the second axle the 0th, 1,2...n pixel each wavelength of corresponding described spectrum respectively, be described the 0th, 1, the 2...n pixel is corresponding one by one with spectral wavelength, thereby between the sequence number of the pixel of the second axle and spectral wavelength, form a kind of corresponding relation, and above-mentioned corresponding relation can adopt formula λ _x=λ ₀+ C ₁X+C ₂X ²+ C ₃X ³Calculate, i.e. x the λ of wavelength for calculating according to above-mentioned formula that pixel is corresponding _x, like this, the wavelength at each pixel place is determined.And the calculating between above-mentioned pixel sequence number and the wavelength is carried out in microprocessor module.

Simultaneously owing to there being m * n pixel array, each pixel of its first axle is labeled as 0 successively, 1...m, each pixel on the second axle is labeled as 0,1 successively, 2...n, therefore arbitrary pixel wherein (m ', x), wherein m '=0,1...m, x=0,1,2...n, this pixel (m ', the x in x) is the sequence number of the pixel of the second axle, can calculate the corresponding wavelength X of this pixel in the processing computing of subsequently microprocessor module by x _x, and m ' is the pixel sequence number of the first axle.So all have m pixel in the everywhere of the second axle, be described the second axle the 0th, 1, the 2...n pixel is in fact the 0th, 1,2...n organizes pixel, in each group, the corresponding Same Wavelength of each pixel, for example, the x place of the second axle has m pixel, and above-mentioned each pixel is corresponding Same Wavelength λ all _x

Simultaneously, what described m * n pixel obtained in fact is the light intensity of the light at each wavelength place in the spectrum, so described spectrum is through behind the photodiode array, because one group of pixel at x place corresponding Same Wavelength λ all _xTherefore the m of this a group pixel has obtained in fact wavelength X _xM the light intensity I at place _xElectric signal, the light intensity I that namely forms at each pixel place in fact _xElectric signal all to coordinate that this pixel should be arranged (m ', x).

The electric signal of the light intensity of the light of each pixel is sent to analog-digital converter through the amplification of signal amplification module conveniently, through analog to digital conversion, electric signal is converted into corresponding digital signal, is about to the light intensity I that each pixel place forms _xElectric signal be converted into digital signal I _x, and each digital signal I _xAll to coordinate that this pixel should be arranged (m ', x).Essence obtained m * n and organize data after analog-digital converter transforms this moment, the corresponding pixel of each group data, each group data all comprise the pixel coordinate (m ', x) with the light intensity I at this pixel place _xThe above-mentioned data of respectively organizing are imported into microprocessor module and are carried out computing subsequently.

In microprocessor module, for m light intensity I of m the pixel at same x place _xData, can adopt average, mean value or the exact value of the light intensity of light that the method such as normal distribution obtains this wavelength place, as the light intensity I of the light at this wavelength place _xIf, the actual photodiode array that adopts m=1, the light intensity that then directly will locate is as the light intensity I of the light at this wavelength place _xLike this, just obtain n group data, in each group data, comprised the light intensity I at pixel the second axial coordinate x and this place _xSubsequently, adopt as mentioned above the formula calculating pixel to put the corresponding wavelength X of the second axial coordinate x _x, and then described n group data are changed into wavelength-light intensity data, namely in each group data, comprise wavelength X _xWith light intensity I _x

Adopt above process, obtain respectively the n group wavelength-light intensity data of the n group wavelength-light intensity data of blank solution, solution to be measured, to Same Wavelength λ _xThe place, employing A '=-lg (I _{To be measured}/ I _Blank), calculating this uncorrected absorbance in wavelength place is A _x', thereby the n that obtains solution to be measured organizes wavelength-absorbance data.

Owing to having obtained the n group wavelength-absorbance data of solution to be measured, namely obtained solution to be measured in the absorbance at each wavelength place, do not carry out the ultraviolet-visible absorption spectroscopy that background interference elimination is proofreaied and correct so can further generate.Adopt subsequently described step 7～10, process and respectively organize wavelength-absorbance data, wavelength-absorbance data after obtaining proofreading and correct, that background interference is eliminated, i.e. wavelength X _xAnd absorbance A _x, and then ultraviolet-visible absorption spectroscopy after the generation correction, that background interference is eliminated.

Background interference elimination method of the present invention, to obtain some groups of pixel electrical signal datas by photoelectric conversion, with the numerical data of obtaining some groups of pixels by analog to digital conversion, the corresponding wavelength of each pixel, the corresponding light intensity of each pixel, thus some groups of wavelength-light intensity datas obtained.Subsequently by contrasting the wavelength-light intensity data of blank solution and solution to be measured, calculate the wavelength-absorbance data of solution to be measured, further proofread and correct for above-mentioned the data formula disclosed in this invention and background interference elimination method, obtain the wavelength-absorbance data after the correction, and generate ultraviolet-visible absorption spectroscopy.

To sum up, the essence of background interference elimination method of the present invention is to rely on photoelectric conversion, analog-to-digital conversion to obtain the data of the absorbance at each wavelength place, correction data subsequently, the spectrum after regeneration is proofreaied and correct, the absorbance at each wavelength place is all through overcorrect in this spectrum.And in traditional detection method, can only obtain the absorbance after the correction at certain several specific wavelengths place, can not obtain the spectrum after the whole correction.Simultaneously background interference elimination method of the present invention is owing to directly adopting raw data to proofread and correct, but not obtains data and proofread and correct by reading spectrogram, so the error of background interference elimination method of the present invention is far smaller than classic method.

To sum up, the ultraviolet-visible absorption spectroscopy after the complete correction that background interference elimination method of the present invention can be obtained, and error is minimum, therefore can be good be applicable to require high material to detect for degree of accuracy, particularly in the drug test.

Simultaneously, it is to be noted, because background interference elimination method of the present invention can be obtained original data subsequently, and proofread and correct accordingly, therefore can be used for the detection of real-time online, obtain real-time raw data, and further obtain real-time ultraviolet-visible absorption spectroscopy, and this also to be traditional detection method can't provide.Traditional detection method adopts existing spectrogram, read the method composing, calculate, and what can obtain is spectrogram and some isolated data of hysteresis sometime.

Below, will be described further by specific embodiment, yet embodiment only being giving an example of alternative embodiment of the present invention, its disclosed feature only is used for explanation and sets forth technical scheme of the present invention, the protection domain that is not intended to limit the present invention.

Description of drawings

Fig. 1 is the schematic diagram of K ratio method.

Fig. 2 a is in the one embodiment of the invention, the ultraviolet-visible absorption spectroscopy that adopts background interference elimination method of the present invention to obtain.

Fig. 2 b is the chart of the material dissolution rate that obtains of the ultraviolet-visible absorption spectroscopy according to Fig. 2 a.

Fig. 2 c is in the another embodiment of the present invention, the ultraviolet-visible absorption spectroscopy that adopts background interference elimination method of the present invention to obtain.

Fig. 2 d is the chart of the material dissolution rate that obtains of the ultraviolet-visible absorption spectroscopy according to Fig. 2 c.

Embodiment

According to claim of the present invention and the disclosed content of instructions, technical scheme of the present invention is specific as follows described:

Embodiment 1:

The background interference elimination method of the ultraviolet-visible absorption spectroscopy of optical fiber in site online drug dissolution of the present invention/dissolution test instrument comprises following steps:

Contain auxiliary material and determinand in the described mixed solution;

According to formula k=A _Measure'/A _Reference', obtain K-ratio k;

In the practical measurement analytic process, at first prepare blank solution and mixed solution, then execution in step 1 is inputted detection light in above-mentioned two kinds of solution.For blank solution, execution in step 2 is inputted and is detected light and gather output light, then with the output light of blank solution through photoelectric conversion, analog-to-digital conversion, obtain the digital signal of the light intensity spectrum of blank solution, namely obtain the data of the light intensity spectrum of one group of statement blank solution.For mixed solution, execution in step 3 is inputted and is detected light and gather output light, then with the output light of mixed solution through photoelectric conversion, analog-to-digital conversion, obtain the digital signal of the light intensity spectrum of mixed solution, namely obtain the data of the light intensity spectrum of one group of statement mixed solution.Adopt subsequently step 4, according to the light intensity spectroscopic data of gained blank solution and mixed solution, obtain the ultraviolet-visible absorption spectroscopy data of mixed solution, and form ultraviolet-visible absorption spectroscopy.

The uv-vis spectra of the auxiliary material solution of described step 5 can obtain by 4 kinds of methods:

In the ultraviolet-visible absorption spectroscopy data of having obtained the ultraviolet-visible absorption spectroscopy data of mixed solution, auxiliary material solution, and call in the standard ultraviolet-visible absorption spectroscopy data of determinand from microprocessor after, adopt step 6～10, ultraviolet-visible absorption spectroscopy data to solution to be measured are proofreaied and correct, eliminate the background interference of auxiliary material, spectroscopic data after obtaining proofreading and correct, and eliminate the ultraviolet-visible absorption spectroscopy of the solution to be measured after auxiliary material disturbs according to above-mentioned data formation.

Embodiment 2:

In embodiment 1, the acquisition process to the light intensity spectroscopic data of blank solution and solution to be measured improves.The background interference elimination method of the ultraviolet-visible absorption spectroscopy of optical fiber in site online drug dissolution of the present invention/dissolution test instrument comprises following steps:

Step 2: generate the light intensity spectral information of blank solution, it is further comprising the steps:

Step 2.5: with the gained digital data transmission to microprocessor module, subsequently according to gained one to one wavelength X and light intensity I _BlankData, generate the light intensity spectrum of blank solution;

Step 3: generate the light intensity spectral information of solution liquid to be measured, it is further comprising the steps:

According to formula k=A _Measure'/A _Reference', obtain K-ratio k;

Embodiment 3:

The step 5 in the modified embodiment 2 in the following ways, other each steps are constant.

In the described step 5, call in the standard ultraviolet-visible absorption spectroscopy of auxiliary material from microprocessor, as the ultraviolet-visible absorption spectroscopy of described auxiliary material solution, thereby obtain the absorbance A at a plurality of one to one different wave length λ place of auxiliary material solution _{Auxiliary material}

Embodiment 4:

Described step 5 is further comprising the steps:

Embodiment 5:

Embodiment 6:

Step 5.1: the standard solution of configuration determinand;

Embodiment 7:

On the basis of embodiment 4, adopt the photodiode array of m * n as described photodiode array module in the present embodiment, m=1～8 wherein, n 〉=128.Each pixel on the first axle of described photodiode array is labeled as 0 successively, 1...m.Each pixel on the second axle of described photodiode array is labeled as 0,1 successively, 2...n.The second axle of described photodiode array is parallel with described grating beam splitting module.Described photodiode array is converted to corresponding electric signal with the light signal that each diode place accepts, thereby obtains the electric signal of corresponding pixel.

The background interference elimination method of the ultraviolet-visible absorption spectroscopy of optical fiber in site online drug dissolution of the present invention/dissolution test instrument comprises step 1～10, and is specific as follows:

Step 1: described light source is to the light of y-type optical fiber input wavelength λ scope at 200～1100nm.

By step 1, in blank solution, mixed solution and auxiliary material solution, input detection light.

To blank solution, employing step 2 gathers the light signal of blank solution and generates the light intensity spectroscopic data of blank solution, and described step 2 may further comprise the steps:

To solution to be measured, employing step 3 gathers the light signal of blank solution and generates the light intensity spectroscopic data of blank solution, and described step 3 may further comprise the steps:

At this moment, obtain light intensity spectrum and the data thereof of the light intensity spectrum of blank solution and data thereof, solution to be measured, adopted subsequently step 4 to be further processed, specific as follows:

In the described step 4, organize one to one wavelength X according to light intensity spectrum, the n of described blank solution _xWith light intensity I _{X is blank}Data, the light intensity spectrum of solution to be measured, n organize one to one wavelength X _xWith light intensity I _{X is to be measured}Data, to the light intensity I of the blank solution at Same Wavelength λ place _BlankLight intensity I with solution to be measured _{To be measured}, employing formula A '=-lg (I _{To be measured}/ I _Blank), calculate mixed solution in the absorbance A of this af at wavelength lambda _Mix

To auxiliary material solution, employing step 5 gathers the light signal of auxiliary material solution and generates the light intensity spectroscopic data of auxiliary material solution, further generates subsequently the ultraviolet-visible absorption spectroscopy of auxiliary material solution, and described step 5 may further comprise the steps:

For choosing of the mensuration wavelength of mixed solution, can choose according to the standard ultraviolet-visible absorption spectroscopy of determinand, specific as follows:

Wherein, in the described step 6, can adopt the standard ultraviolet-visible absorption spectroscopy of determinand, choose the mensuration wavelength of determinand as the mensuration wavelength X of mixed solution _Measure

Preferably, adopt point-to-point comparison method, obtain the reference absorbance A _Ref, to reduce correction error.In the described step 6, organize one to one wavelength X according to ultraviolet-visible absorption spectroscopy and the n of solution to be measured _xAnd absorbance A _{X mixes}Data, wavelength X relatively successively ₁, λ ₂, λ ₃... λ _nLocate corresponding absorbance A _{Mix 1}, A _{Mix 2}, A _{Mix 3}... A _{Mix n}, choosing wherein, maximum absorbance is labeled as A _Max, the corresponding wavelength of this absorbance of mark is for measuring wavelength X _Measure

At this moment, the ultraviolet-visible absorption spectroscopy data of mixed solution, ultraviolet-visible absorption spectroscopy data and the mensuration wavelength X of auxiliary material solution have been obtained _Measure, adopt each spectroscopic data of step 7～10 pair mixed solution to proofread and correct, to eliminate background interference.

As shown in Figure 1, to adopt K ratio method to process the principle schematic of proofreading and correct spectroscopic data, the b line is the ultraviolet-visible absorption spectroscopy of auxiliary material among the figure, the a+b line is the ultraviolet-visible absorption spectroscopy of uncorrected mixed solution, it need to eliminate background interference, to obtain the ultraviolet-visible absorption spectroscopy of the determinand that does not have background interference, shown in a line.According to Fig. 1, below adopt step 7～10 to process the correction spectroscopic data.

Adopt step 7, to obtain reference wavelength λ _Reference, described step 7 is further comprising the steps:

According to the mensuration wavelength X of having obtained _MeasureWith reference wavelength λ _Reference, adopt step 8 to obtain auxiliary material solution in the absorbance at above-mentioned two wavelength places, described step 8 is further comprising the steps:

Step 8.3: according to formula k=A _Measure'/A _Reference', obtain K-ratio k.

According to the mensuration wavelength X of having obtained _MeasureWith reference wavelength λ _Reference, adopt step 9 to obtain mixed solution in the absorbance at above-mentioned two wavelength places, described step 9 is further comprising the steps:

Measuring wavelength X according to the K-ratio k that has obtained and mixed solution _MeasureWith reference wavelength λ _ReferenceThe absorbance A at place _Measure" and A _Reference", adopt step 10 to proofread and correct mixed solution and measuring wavelength X _MeasureThe absorbance A at place _MeasureThereby, eliminate the background interference at this place, specific as follows:

So far, the be eliminated determinand of background interference is being measured wavelength X _MeasureThe absorbance A at place _Measure, trimming process finishes.

Embodiment 8:

In embodiment 7, obtained determinand and measured wavelength X _MeasureThe absorbance A at place _MeasureIn addition, can also adopt above-mentioned formula, further proofread and correct the ultraviolet-visible absorption spectroscopy of mixed solution, obtaining the spectrum of eliminating after the background interference, in order to realize this purpose, background interference elimination method of the present invention is on the basis of the step 1 of embodiment 7～10, further comprise step 11, described step 11 is further comprising the steps:

So far, the ultraviolet-visible absorption spectroscopy of the determinand after the background interference that is eliminated and data thereof, trimming process finishes.

Embodiment 9:

Adopt following technical parameter modified embodiment 7 and embodiment 8.Each step among embodiment 7 and the embodiment 8 is constant, be the photodiode array module that adopts be the photodiode array of m * n, m=2 wherein, n=2 ^t, t 〉=7, n 〉=128.

Embodiment 10:

Adopt following technical parameter modified embodiment 7 and embodiment 8.Each step among embodiment 7 and the embodiment 8 is constant, be the photodiode array module that adopts be the photodiode array of m * n, m=3 wherein, n=2 ^t, t 〉=7, n 〉=128.

Embodiment 11:

Adopt following technical parameter modified embodiment 7 and embodiment 8.Each step among embodiment 7 and the embodiment 8 is constant, be the photodiode array module that adopts be the photodiode array of m * n, m=5 wherein, n=2 ^t, t 〉=7, n 〉=128.

Embodiment 12:

Adopt following technical parameter modified embodiment 7 and embodiment 8.Each step among embodiment 7 and the embodiment 8 is constant, be the photodiode array module that adopts be the photodiode array of m * n, m=1 wherein, n=n=128,256,1024,2048 or 4096.Along the second axle of described photodiode array, successively the sequence number x of each pixel of mark be 0,1,2...n.

Embodiment 13:

Adopt the method described in the embodiment 12, measure the drug dissolution of ibuprofen sustained release capsules.

The specification of the ibuprofen sustained release capsules that adopts is 0.3g, according to 2005 editions Chinese Pharmacopoeia drug release determination methods [appendix XD first method], take phosphate buffer (the pH value should be 6.0 ± 0.05) 900ml as release medium, rotating speed is that per minute 30 turns, 7 hours release time.The reference substance solution of configuration brufen configures corresponding blank solution as solution to be measured.

Get one of ibuprofen sustained release capsules, after exenterating, get the hungry area softgel shell and be dissolved in phosphate buffer (pH6.0), configuration auxiliary material solution.

Get six of ibuprofen sustained release capsules and place phosphate buffer, carry out Dissolution Rate Testing, the solution of the real-time stripping of process of the test Chinese traditional medicine does not need dissolution fluid is taken out from digestion instrument as mixed solution.

Execution in step 1 is inputted detection light in blank solution and solution to be measured.

Execution in step 2 is obtained the light signal of blank solution, and records the light intensity spectroscopic data of blank solution in detection module.

Execution in step 3 is obtained the light signal of solution to be measured, and records the light intensity spectroscopic data of solution to be measured in detection module.

Execution in step 4 in microprocessor module, is obtained the spectroscopic data of the ultraviolet-visible absorption spectroscopy of solution to be measured.

Execution in step 5 is obtained the light signal of auxiliary material solution, and records the light intensity spectroscopic data of auxiliary material solution in detection module, in microprocessor module, obtains the spectroscopic data of the ultraviolet-visible absorption spectroscopy of auxiliary material solution subsequently.

Step 6: call in the standard ultraviolet-visible absorption spectroscopy of determinand from microprocessor module, choose the mensuration wavelength X _Measure

Step 7: call in the standard ultraviolet-visible absorption spectroscopy of determinand and the ultraviolet-visible absorption spectroscopy of gained auxiliary material solution from microprocessor module, select reference wavelength λ _Reference

Step 8: in microprocessor module, according to the spectroscopic data of the ultraviolet-visible absorption spectroscopy of gained auxiliary material solution, obtain auxiliary material solution and measuring wavelength X _MeasureWith reference wavelength λ _ReferenceThe absorbance A at place _Measure' and A _Reference', according to formula k=A _Measure'/A _Reference', obtain K-ratio k.

Step 9: in microprocessor module, according to the spectroscopic data of the ultraviolet-visible absorption spectroscopy of gained mixed solution, obtain mixed solution and measuring wavelength X _MeasureWith reference wavelength λ _ReferenceThe absorbance A at place _Measure" and A _Reference".

Step 10: in microprocessor module, according to formula A _Measure=A _Measure"-kA _Reference", the mixed solution that obtains containing determinand and auxiliary material is after the interference of eliminating auxiliary material, and determinand is wherein being measured wavelength X _MeasureThe absorbance A at place _Measure

In actual testing process, can configure the reference substance solution of brufen of one group of variable concentrations as solution to be measured and corresponding auxiliary material solution, to each solution to be measured and auxiliary material solution execution in step 1～8 respectively, obtain measuring wavelength and K-ratio k.The light signal of each solution to be measured of replicate determination also obtains the ultraviolet-visible absorption spectroscopy of each solution to be measured, and shown in Fig. 2 a, shown in the figure is the ultraviolet-visible absorption spectroscopy of brufen reference substance.By this spectrum, determine to measure wavelength.The light signal of each auxiliary material solution of replicate determination also obtains the ultraviolet-visible absorption spectroscopy of auxiliary material solution, and shown in Fig. 2 b, shown in the figure is the absorption spectrum of ibuprofen capsule softgel shell.By this spectrum, Coefficient of determination multiplying power k.

In actual testing process, described one group of mixed solution that concentration is different is followed process in leaching, in different time points, gather the ultraviolet-visible absorption spectroscopy of respective concentration, such as Fig. 2 c, be depicted as the ultraviolet-visible absorption spectroscopy of ibuprofen sustained release capsules stripping in the time of 420 minutes.According to this absorption spectrum, to proofread and correct and obtain the concentration of the solution to be measured at this time point place, thereby obtained the concentration curve that each solution to be measured changed along with the time, i.e. dissolution rate curve is shown in Fig. 2 d.

Because the method disclosed in the present can real-time online gathers, detection and background interference elimination are proofreaied and correct, therefore can be used for the real-time detection of process in leaching and generate dissolution rate curve shown in Fig. 2 d.And classic method can only be obtained the isolated data at indivedual time points place, can't generate complete dissolution rate curve.

Foregoing is exemplifying of specific embodiments of the invention, for the wherein not equipment of detailed description and structure, should be understood to take the existing common apparatus in this area and universal method to be implemented.

Claims

1. the background interference elimination method of the ultraviolet-visible absorption spectroscopy of optical fiber in site online drug dissolution/dissolution test instrument, described optical fiber in site online drug dissolution/dissolution test instrument comprises digestion instrument, the light source that links to each other successively, y-type optical fiber, detection module and microprocessor module, described y-type optical fiber connects light source simultaneously, detection module and digestion instrument, described detection module comprises the grating beam splitting module that links to each other successively, the photodiode array module, signal amplification module and analog-digital converter, described microprocessor is for the treatment of data and store uv-vis spectra standard spectrogram, it is characterized in that, the background interference elimination method of described uv-vis spectra comprises following steps:

Contain auxiliary material and determinand in the described mixed solution;

Step 4: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, the light intensity spectrum of mixed solution, a plurality of one to one different wave length λ place light intensity I _Mix, adopt formula A in each af at wavelength lambda _Mix=-Ig (I _Mix/ I _Blank), calculate mixed solution in the absorbance of each af at wavelength lambda, obtain the absorbance A to be corrected at a plurality of one to one different wave length λ place _MixThereby, obtain the ultraviolet-visible absorption spectroscopy of mixed solution;

Step 6: call in the standard ultraviolet-visible absorption spectroscopy of determinand from microprocessor, choose the mensuration wavelength of determinand as the mensuration wavelength X of mixed solution _Measure, perhaps according to the ultraviolet-visible absorption spectroscopy of mixed solution, compare successively the absorbance A of each af at wavelength lambda _Mix, determine the wavelength that maximum absorption band is corresponding, choose it as measuring wavelength X _Measure

According to formula k=A _Measure'/A _Reference', obtain K-ratio k;

2. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1 is characterized in that, described step 2 is further comprising the steps:

3. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1 is characterized in that, described step 3 is further comprising the steps:

4. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1, it is characterized in that, in the described step 5, call in the standard ultraviolet-visible absorption spectroscopy of auxiliary material from microprocessor, as the ultraviolet-visible absorption spectroscopy of described auxiliary material solution, thereby obtain the absorbance A at a plurality of one to one different wave length λ place of auxiliary material solution _{Auxiliary material}

5. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1 is characterized in that, described step 5 is further comprising the steps:

Step 5.6: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, the light intensity spectrum of auxiliary material solution, a plurality of one to one different wave length λ place light intensity I _{Auxiliary material}, adopt formula A in each af at wavelength lambda _{Auxiliary material}=-Ig (I _{Auxiliary material}/ I _Blank), calculate auxiliary material solution in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Auxiliary material}Thereby, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

6. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1 is characterized in that, described step 5 is further comprising the steps:

7. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 1 is characterized in that, described step 5 is further comprising the steps:

Step 5.1: the standard solution of configuration determinand;

Step 5.7: according to the light intensity I at the light intensity spectrum of described blank solution, a plurality of one to one different wave length λ place _Blank, determinand the light intensity spectrum, the light intensity I at a plurality of one to one different wave length λ place of standard solution _{Standard is to be measured}, adopt formula A in each af at wavelength lambda _{Standard is to be measured}=-Ig (I _{Standard is to be measured}/ I _Blank), calculate the standard solution of determinand in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Standard is to be measured}

Step 5.8: according to the absorbance A to be corrected at a plurality of one to one different wave length λ place of gained mixed solution in the step 4 _Mix, the absorbance A at a plurality of one to one different wave length λ place of the standard solution of step 5.7 gained determinand _Mark _{Accurate to be measured}, according to formula A _{Auxiliary material}=A _Mix-A _{Standard is to be measured}, calculate auxiliary material solution in the absorbance of each af at wavelength lambda, obtain the absorbance A at a plurality of one to one different wave length λ place _{Auxiliary material}Thereby, obtain the ultraviolet-visible absorption spectroscopy of auxiliary material solution.

8. such as the disposal route of the described ultraviolet-visible absorption spectroscopy of claim 1～7, it is characterized in that, described photodiode array module is the photodiode array of m * n, m=1～8 wherein, n 〉=128;

Each pixel on the first axle of described photodiode array is labeled as 0 successively, 1...m;

Each pixel on the second axle of described photodiode array is labeled as 0,1 successively, 2...n;

The second axle of described photodiode array is parallel with described grating beam splitting module;

Described photodiode array is converted to corresponding electric signal with the light signal that each diode place accepts, thereby obtains the electric signal of corresponding pixel.

9. the bearing calibration of ultraviolet-visible absorption spectroscopy as claimed in claim 8 is characterized in that, described photodiode array module is the photodiode array of m * n, m=1 wherein, n=128,256,1024,2048,4096; Along the second axle of described photodiode array, successively the sequence number x of each pixel of mark be 0,1,2...n.

10. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 9 is characterized in that, described step 2 is further comprising the steps:

Wherein, x is the sequence number of pixel, λ _xBe the light wavelength at this pixel place, λ ₀Be the light wavelength at the 0th pixel place, C ₁, C ₂And C ₃Be the coefficient relevant with wavelength resolution;

11. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 10 is characterized in that, described step 3 is further comprising the steps:

12. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 11 is characterized in that, in the described step 4, organizes one to one wavelength X according to light intensity spectrum, the n of described blank solution _xWith light intensity I _{X is blank}Data, the light intensity spectrum of solution to be measured, n organize one to one wavelength X _xWith light intensity I _{X is to be measured}Data, to the light intensity I of the blank solution at Same Wavelength λ place _BlankLight intensity I with solution to be measured _{To be measured}, employing formula A '=-Ig (I _{To be measured}/ I _Blank), calculate mixed solution in the absorbance A of this af at wavelength lambda _Mix

13. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 12 is characterized in that, described step 5 is further comprising the steps:

Step 5.7: light intensity spectrum, n according to described blank solution organize one to one wavelength X _xWith light intensity I _{X is blank}Data, the light intensity spectrum of auxiliary material solution, n organize one to one wavelength X _xWith light intensity I _{The x auxiliary material}Data, to the light intensity I of the blank solution at Same Wavelength λ place _BlankLight intensity I with solution to be measured _{Auxiliary material}, employing formula A '=-Ig (I _{Auxiliary material}/ I _Blank), calculate mixed solution in the absorbance A of this af at wavelength lambda _{Auxiliary material}

14. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 13 is characterized in that, adopts the standard ultraviolet-visible absorption spectroscopy of determinand in the step 6, chooses the mensuration wavelength of determinand as the mensuration wavelength X of mixed solution _Measure

15. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 13 is characterized in that, adopts the ultraviolet-visible absorption spectroscopy of mixed solution to determine to measure wavelength X in the step 6 _Measure, it is further comprising the steps:

Ultraviolet-visible absorption spectroscopy and n according to solution to be measured organize one to one wavelength X _xAnd absorbance A _{X mixes}Data, wavelength X relatively successively ₁, λ ₂, λ ₃... λ _nLocate corresponding absorbance A _{Mix 1}, A _{Mix 2}, A _{Mix 3}... A _{Mix n}, choosing wherein, the absorbance of maximum absorption band is labeled as A _Max, the corresponding wavelength of this absorbance of mark is for measuring wavelength X _Measure

16. the disposal route such as claim 13,14 described ultraviolet-visible absorption spectroscopies is characterized in that, described step 7 is further comprising the steps:

Step 7.1: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _x _{Auxiliary material}Data, from λ ₁, λ ₂, λ ₃... λ _nIn filter out A _{Auxiliary material 1}, A _{Auxiliary material 2}, A _{Auxiliary material 3}... A _{Auxiliary material n}In greater than the corresponding wavelength X of 0.01 absorbance ';

Step 7.3: in each wavelength X of gained " in, compare successively each λ " corresponding absorbance A ', choose maximal value A ' _MaxA corresponding wavelength is as reference wavelength λ _Reference

17. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 16 is characterized in that, described step 8 is further comprising the steps:

Step 8.1: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _x _{Auxiliary material}Data, determine λ _MeasureCorresponding absorbance A _Measure';

Step 8.2: ultraviolet-visible absorption spectroscopy and n according to auxiliary material solution organize one to one wavelength X _xAnd absorbance A _x _{Auxiliary material}Data, determine λ _ReferenceCorresponding absorbance A _Reference';

Step 8.3: according to formula k=A _Measure'/A _Reference', obtain K-ratio k.

18. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 17 is characterized in that, described step 9 is further comprising the steps:

Step 9.1: ultraviolet-visible absorption spectroscopy and n according to mixed solution organize one to one wavelength X _xAnd absorbance A _Mixed _CloseData, determine λ _MeasureCorresponding absorbance A _Measure";

Step 9.2: ultraviolet-visible absorption spectroscopy and n according to mixed solution organize one to one wavelength X _xAnd absorbance A _Mixed _CloseData, determine λ _ReferenceCorresponding absorbance A _Reference".

19. the disposal route of ultraviolet-visible absorption spectroscopy as claimed in claim 18 is characterized in that, further comprises step 11, described step 11 is further comprising the steps:

Step 11.1: ultraviolet-visible absorption spectroscopy and n according to the gained mixed solution organize one to one wavelength X _xAnd absorbance A _MixData, adopt formula A=A _Mix-kA _Reference", proofread and correct successively each wavelength X ₁, λ ₂, λ ₃... λ _nCorresponding each absorbance A _{Mix 1}, A _{Mix 2}, A _{Mix 3}..A _{Mix n}, the absorbance A after obtaining proofreading and correct ₁, A ₂, A ₃... A _n, the mixed solution that namely obtains containing determinand and auxiliary material is after the interference of eliminating auxiliary material, and determinand wherein is in the absorbance A of each af at wavelength lambda;