CN101101260A - Near infrared spectrum damage-free analysis method for anti-tuberculosis drugs - Google Patents
Near infrared spectrum damage-free analysis method for anti-tuberculosis drugs Download PDFInfo
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- CN101101260A CN101101260A CN 200710055682 CN200710055682A CN101101260A CN 101101260 A CN101101260 A CN 101101260A CN 200710055682 CN200710055682 CN 200710055682 CN 200710055682 A CN200710055682 A CN 200710055682A CN 101101260 A CN101101260 A CN 101101260A
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Abstract
The invention discloses method of testing effective constituent of near infrared light detection anti tubercular agent. Using the basis of anti tubercular agent action spectrum near infrared light and the measurand information, getting effective constituent (rifampicin,isoniazide or pyrazinamide ) of which by anti tubercular agent action spectrum near infrared light and their background information; achieving the lossless detection the content of effective constituent (rifampicin,isoniazide or pyrazinamide ) in the anti tubercular agent near infrared light complex background by the multi element normalized method of chemometrics. It settles the problem of high cost, long period, medicament cannot use after analyzing etc when analyzing the anti tubercular agent effective constituent in existence, establishing the fast, high pass mete, lossless and needed on-line analysis green medicament analytic method for the anti tubercular agent. The advantages is that the sample pre-processing is easy, the detection is fast and undamaged, the detection time of each sample is shortage of two min; the result is credibility, the error is less than5%.
Description
Technical field
The present invention discloses a kind of method of near infrared spectrum nondestructive analysis antituberculotic, and the quick nondestructive that relates to active constituent content in the antituberculotic detects, and belongs to the drug test analysis technical field.
Background technology
Tuberculosis is the main diseases that causes death of single infection therefore, annual neopathy 800～1,000 ten thousand, and annual because of dead 200～3,000,000 people of tuberculosis, tuberculosis is all more than any infectious disease to the death that the teenager causes.Rimactazid and pyrazinamide are relatively effectively medicines of present approach.
At present, composition in the antituberculotic and background complexity, need such as the conventional determining method reversed phase high efficiency chromatography of effective constituent Rimactazid and pyrazinamide, thin layer chromatography carry out separation determination to the composition of sample, and complex operation is time-consuming, and need a large amount of organic reagents.Can not satisfy the needs that quick nondestructive is analyzed.
Summary of the invention
The present invention discloses a kind of method of near infrared spectrum nondestructive analysis antituberculotic, sample does not need pre-treatment, can realize high flux, online nondestructive analysis, and the result accurately and reliably, error is less than 5%, solved the loaded down with trivial details problem such as time-consuming of existing antituberculotic detecting operation.
Technical solution of the present invention is as follows:
Utilize to comprise the principal ingredient of sample and information to be measured in the antituberculotic near infrared spectrum, compose with the antituberculotic near infrared light and can obtain wherein effective constituent (Rimactazid pyrazinamide) and their background information; Utilize the method for polynary correction in the Chemical Measurement to realize the content of non-destructive determination effective constituent from the near infrared spectrum complex background of antituberculotic (Rimactazid or pyrazinamide).
The present invention selects the spectrum district and the suitable preprocessing procedures that are fit to, with the method for the polynary correction of chemical metrology set up sample the near infrared light spectrum signature and to be measured between mathematical model, utilize this mathematical model as long as the near infrared spectrum of non-destructive determination antituberculotic can be determined the content of its effective constituent (Rimactazid or pyrazinamide).
The polynary correction of the Chemical Measurement that adopts among the present invention is partial least square method and artificial neural network algorithm to the algorithm of continuous wavelength near infrared spectrum.Preprocess method to spectrum comprises first order derivative, second derivative, Fourier transform, convolution is smooth and wavelet transformation etc.
The following step of concrete employing:
1) sampling: collect antituberculotic;
2) mensuration of sample near infrared spectrum: with the direct embedded blank plate of sample central authorities, with BaSO
4As blank, place near infrared detection instrument integrating sphere sample cell, obtain the antituberculotic abosrption spectrogram by computerized near infrared scan, write down the absorption spectrum of various samples in the near infrared spectrum district;
3) sample effective constituent determination: adopt high effective liquid chromatography for measuring sample content of effective;
4) foundation of mathematical model: use multivariate calibration methods, set up the mathematical model of the relation between the content of effective and absorption spectrum in the sample;
5) verification of model: get the antituberculotic of known active constituent content, the same terms is measured near-infrared absorption spectrum down, according to the content of effective in the polynary correction calculated with mathematical model sample of having set up, requires error less than 5%;
6) analysis of testing sample: behind the testing sample scanning near infrared spectrum, calculate content of effective by spectrometer with corresponding mathematical model.
Described antituberculotic is selected from one or more in rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and the different good fortune acid amides sheet, and the effective constituent of medicine comprises Rimactazid or pyrazinamide.
The condition determination of standard model spectrum is: wavelength 800～2500nm, spectral band-width width are 12nm.
The computing machine calculation is the multivariate calibration methods that utilizes Chemical Measurement.
The polynary correction of adopting of Chemical Measurement is partial least square method or artificial neural network algorithm to the continuous wavelength near infrared spectrum
Preprocessing procedures comprises first order derivative, second derivative, Fourier transform, convolution is smooth and wavelet transformation.
Advantage of the present invention: to quick, the harmless detection of active constituent content in the antituberculotic, sample need not pre-treatment, can on-the-spotly detect, utilize the near infrared spectrum view to measure, the less than 1 minute detection time of each sample, reliable results, error is less than 5%.For realizing to medicine that harmless and online quick nondestructive detects, pharmaceutical production department and national drug administrative authority provide technical foundation.
Description of drawings
The near infrared light spectrogram of five kinds of antituberculotic rifampicin tabletses of Fig. 1, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and 236 samples of different good fortune acid amides sheet;
Fig. 2 is the illustraton of model of the rifampin that adopts modeling of the present invention and obtain;
Fig. 3 is the illustraton of model of the isoniazid of adopting modeling of the present invention and obtaining;
Fig. 4 is the illustraton of model of the pyrazinamide that adopts modeling of the present invention and obtain;
Embodiment
By following examples the present invention is described for example further, and do not limit the present invention in any way, under the prerequisite that does not deviate from technical solution of the present invention, any change or change that those of ordinary skills that the present invention did are realized easily all will fall within the claim scope of the present invention.
Embodiment 1
Measure the content of rifampin in the rifampicin tablets:
Collect the Inner Mongol
*50 of the rifampicin tabletses of medicine company are as testing sample, batch number: 031123.With rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and five kinds of antituberculotics of different good fortune acid amides sheet, totally 236 samples are as modeling sample.
Sample is pulverized dissolving, adopt high-efficient liquid phase technique to measure the content of effective constituent rifampin in the rifampicin tablets.
The rifampicin tablets sample is embedded in blank plate central authorities, puts near-infrared spectrometer integrating sphere sample cell, adopting spectral wavelength by model analysis is 1500～2000nm, and the spectral band-width width is chosen as 12nm, writes down the absorption spectrum of each sample in the near infrared spectrum district.See Fig. 1.
Use partial least square method, set up the mathematical model that concerns between the content of rifampin in the sample and the absorption spectrum.
Referring to Fig. 2, rifampin model prediction related coefficient shown in Figure 2 is 0.9864, validation-cross root mean square 0.0494, predicted root mean square error 0.0182.
Verification of model: the sample of getting known different rifampin content, measure the absorption spectrum of its near-infrared region under the same conditions, according to the rifampin content in the partial least square method Quantitative Analysis Model calculation sample of having set up, require error less than 5%, compare with the standard method measurement result, fitting related coefficient is 0.985～0.999.
With the content of rifampin and the mean deviation of actual value in the corresponding mathematical model measurement testing sample is 1.08%.
Embodiment 2
Measure the content of isoniazid in the isoniazid tablets:
Collect Chengdu
*40 of the isoniazid tabletses of medicine company are as testing sample, batch number: 041005.With rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and five kinds of antituberculotics of different good fortune acid amides sheet, totally 236 samples are as modeling sample.
Sample is pulverized dissolving, adopt high-efficient liquid phase technique to measure the content of effective constituent isoniazid in the isoniazid tablets.
The isoniazid tablets sample is embedded in blank plate central authorities, puts near-infrared spectrometer integrating sphere sample cell, adopting spectral wavelength by model analysis is 1500～2000nm, and the spectral band-width width is chosen as 12nm, writes down the absorption spectrum of each sample in the near infrared spectrum district.See Fig. 1.
Use partial least square method, set up the mathematical model that concerns between the content of isoniazid in the sample and the absorption spectrum.
Get the sample of known different isoniazid content, measure the absorption spectrum of its near-infrared region under the same conditions, according to the isoniazid in the partial least square method Quantitative Analysis Model calculation sample of having set up, require error less than 5%, compare with the standard method measurement result, fitting related coefficient is 0.985～0.999.
Referring to Fig. 3, isoniazid illustraton of model prediction related coefficient 0.9989 shown in Figure 3, validation-cross root mean square 0.0257, predicted root mean square error 0.0166.
With the content of isoniazid and the mean deviation of actual value in the corresponding mathematical model measurement testing sample is 0.23%.
Embodiment 3
Measure the content of Rimactazid and pyrazinamide in the different good fortune acid amides:
Collect the North China pharmacy
*48 of the different good fortune sheets of company limited are as testing sample, and with rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and five kinds of antituberculotics of different good fortune acid amides sheet, totally 236 samples are as modeling sample.
Sample is pulverized dissolving, adopt high-efficient liquid phase technique to measure the content of effective constituent Rimactazid and pyrazinamide in the different good fortune acid amides.
Different good fortune acid amides sample is embedded in blank plate central authorities, puts near-infrared spectrometer integrating sphere sample cell, adopting spectral wavelength by model analysis is 1300～2500nm, and the spectral band-width width is chosen as 12nm, writes down the absorption spectrum of each sample in the near infrared spectrum district.See Fig. 1.
Use radial base neural net, set up the mathematical model that concerns between the content of Rimactazid and pyrazinamide in the sample and the absorption spectrum.
Get the known different Rimactazids and the sample of pyrazinamide content, measure the absorption spectrum of its near-infrared region under the same conditions, according to Rimactazid and the pyrazinamide in the radial base neural net Quantitative Analysis Model calculation sample of having set up, require error less than 5%, compare with the standard method measurement result, fitting related coefficient is 0.985～0.999.
Referring to Fig. 2, rifampin model prediction related coefficient 0.9864 shown in Figure 2, validation-cross root mean square 0.0494, predicted root mean square error 0.0182.
Referring to Fig. 3, isoniazid illustraton of model prediction related coefficient 0.9989 shown in Figure 3, validation-cross root mean square 0.0257, predicted root mean square error 0.0166.
Referring to Fig. 4, pyrazinamide illustraton of model prediction related coefficient 0.9993 shown in Figure 4, validation-cross root mean square 0.0307, predicted root mean square error 0.0134.
The analysis of testing sample: record with corresponding mathematical model that Rimactazid and the content of pyrazinamide and the mean deviation of actual value are respectively 0.92%, 0.65% and 0.41% in the testing sample.
Embodiment 4
Measure the content of pyrazinamide in the pyrazinamide tablet:
Collect Shenyang
*35 of the pyrazinamide tablets of pharmaceutical Co. Ltd are as testing sample, batch number: 0409111.With rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and five kinds of antituberculotics of different good fortune acid amides sheet (totally 236 samples) as modeling sample.
Sample is pulverized dissolving, adopt high-efficient liquid phase technique to measure the content of effective constituent pyrazinamide in the pyrazinamide tablet.
The pyrazinamide tablet sample is embedded in blank plate central authorities, put near-infrared spectrometer integrating sphere sample cell, adopting spectral wavelength by model analysis is 1500～2000nm, and the spectral band-width width is chosen as 12nm, writes down the absorption spectrum of each sample in the near infrared spectrum district.See Fig. 1.
Use partial least square method, set up the mathematical model that concerns between the content of pyrazinamide in the sample and the absorption spectrum.
Get the sample of known different pyrazinamide content, measure the absorption spectrum of its near-infrared region under the same conditions, according to the pyrazinamide in the partial least square method Quantitative Analysis Model calculation sample of having set up, require error less than 5%, compare with the standard method measurement result, fitting related coefficient is 0.985～0.999.
Referring to Fig. 4, pyrazinamide illustraton of model prediction related coefficient 0.9993 shown in Figure 4, validation-cross root mean square 0.0307, predicted root mean square error 0.0134.
With the content of pyrazinamide and the mean deviation of actual value in the corresponding mathematical model measurement testing sample is 0.59%.
Embodiment 5
Measure the content of rifampin and isoniazid in the different good fortune sheet:
Collect the North China pharmacy
*38 of the different good fortune sheets of company limited are as testing sample, with rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and five kinds of antituberculotics of different good fortune acid amides sheet (totally 236 samples) as modeling sample.
Sample is pulverized dissolving, the content of effective constituent rifampin and isoniazid in the employing high-efficient liquid phase technique measurement isoniazid tablets.
The isoniazid tablets sample is embedded in blank plate central authorities, puts near-infrared spectrometer integrating sphere sample cell, adopting spectral wavelength by model analysis is 1300～2500nm, and the spectral band-width width is chosen as 12nm, writes down the absorption spectrum of each sample in the near infrared spectrum district.
Use radial base neural net, set up the mathematical model that concerns between the content of rifampin and isoniazid in the sample and the absorption spectrum.
Get the known different rifampins and the sample of isoniazid content, measure the absorption spectrum of its near-infrared region under the same conditions, according to the rifampin in the radial base neural net Quantitative Analysis Model calculation sample of having set up and the content of isoniazid, require error less than 5%, compare with the standard method measurement result, fitting related coefficient is 0.985～0.999.
Referring to Fig. 2, rifampin model prediction related coefficient 0.9864 shown in Figure 2, validation-cross root mean square 0.0494, predicted root mean square error 0.0182.
Referring to Fig. 3, isoniazid illustraton of model prediction related coefficient 0.9989 shown in Figure 3, validation-cross root mean square 0.0257, predicted root mean square error 0.0166.
The analysis of testing sample: record with corresponding mathematical model that rifampin and the content of isoniazid and the mean deviation of actual value are respectively 0.88% and 0.34% in the testing sample.
Claims (6)
1, a kind of antituberculotic near infrared quick non-destructive detection method is characterized in that:
1) sampling: collect antituberculotic;
2) mensuration of sample near infrared spectrum: with the direct embedded blank plate of sample central authorities, with BaSO
4As blank, place near infrared detection instrument integrating sphere sample cell, obtain the antituberculotic abosrption spectrogram by computerized near infrared scan, write down the absorption spectrum of various samples in the near infrared spectrum district;
3) sample effective constituent determination: adopt high effective liquid chromatography for measuring sample content of effective;
4) foundation of mathematical model: use multivariate calibration methods, set up the mathematical model of the relation between the content of effective and absorption spectrum in the sample;
5) verification of model: get the antituberculotic of known active constituent content, the same terms is measured near-infrared absorption spectrum down, according to the content of effective in the polynary correction calculated with mathematical model sample of having set up, requires error less than 5%;
6) analysis of testing sample: behind the testing sample scanning near infrared spectrum, calculate content of effective by spectrometer with corresponding mathematical model.
2, the method for near infrared spectrum nondestructive analysis antituberculotic according to claim 1, it is characterized in that: antituberculotic is selected from one or more in rifampicin tablets, isoniazid tablets, pyrazinamide tablet, different good fortune sheet and the different good fortune acid amides sheet, and the effective constituent of medicine comprises Rimactazid or pyrazinamide.
3, the method for near infrared spectrum nondestructive analysis antituberculotic according to claim 1 is characterized in that the condition determination of standard model spectrum is: wavelength 800～2500nm, the spectral band-width width of sample measurement is 12nm.
4, the near infrared quick non-destructive detection method of antituberculotic according to claim 1 is characterized in that: the computing machine calculation is the multivariate calibration methods that utilizes Chemical Measurement.
5, the method for near infrared spectrum nondestructive analysis antituberculotic according to claim 1 is characterized in that: the polynary correction of the Chemical Measurement of employing comprises that to the continuous wavelength near infrared spectrum be partial least square method or artificial neural network algorithm
6, the method for near infrared spectrum nondestructive analysis antituberculotic according to claim 1 is characterized in that: preprocessing procedures comprises first order derivative, second derivative, Fourier transform, convolution is smooth and wavelet transformation.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101915744A (en) * | 2010-07-05 | 2010-12-15 | 北京航空航天大学 | Near infrared spectrum nondestructive testing method and device for material component content |
| CN102768193A (en) * | 2011-05-04 | 2012-11-07 | 中国科学技术大学 | Infrared spectroscopic method for rapid determination of storage substance content in activated sludge cell |
| CN103674884A (en) * | 2012-09-17 | 2014-03-26 | 福建中烟工业有限责任公司 | Random forest classification method for tobacco leaf style characteristics based on near infrared spectral information |
| CN105784951A (en) * | 2014-12-24 | 2016-07-20 | 九芝堂股份有限公司 | Multiple indicator rapid detection method for raw medicinal powder of condensed pill of six drugs with rehmannia |
-
2007
- 2007-05-25 CN CN 200710055682 patent/CN101101260A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101915744A (en) * | 2010-07-05 | 2010-12-15 | 北京航空航天大学 | Near infrared spectrum nondestructive testing method and device for material component content |
| CN102768193A (en) * | 2011-05-04 | 2012-11-07 | 中国科学技术大学 | Infrared spectroscopic method for rapid determination of storage substance content in activated sludge cell |
| CN103674884A (en) * | 2012-09-17 | 2014-03-26 | 福建中烟工业有限责任公司 | Random forest classification method for tobacco leaf style characteristics based on near infrared spectral information |
| CN105784951A (en) * | 2014-12-24 | 2016-07-20 | 九芝堂股份有限公司 | Multiple indicator rapid detection method for raw medicinal powder of condensed pill of six drugs with rehmannia |
| CN105784951B (en) * | 2014-12-24 | 2019-03-29 | 九芝堂股份有限公司 | A kind of Liuwei Dihuang Wan condensed pill crude drug powder multiple index quick detecting method |
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