CN102147360B - Detection method for drug combination - Google Patents
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Abstract
The invention discloses a method for detecting the content of acetaminophen and moisture in a drug combination (999 Ganmaoling particles) for treating influenza by using near infrared spectrums; a corresponding acetaminophen content model and a corresponding water content model are established; a chemical method proves that the deviation of cross validation is very small; and the invention confirms that the method for determining the content of components in the drug combination (999 Ganmaoling particles) by adopting a near infrared spectrometer and configuring an integrating sphere diffuse reflection module is achievable.
Description
Technical field
The present invention relates to a kind of detection method of medicine, particularly relate to the method for utilizing near infrared spectrum to detect a kind of pharmaceutical composition.
Background technology
Near infrared (NIR) spectrometer is a kind of quick, harmless, pollution-free, green analytical approach, and near infrared spectrum information is mainly derived from frequency multiplication and the sum of fundamental frequencies absorption of vibrations that C-H in the molecule, N-H, O-H, S-H etc. contain hydrogen group.(MIR) is the same with middle infrared spectrum, all organism all have corresponding characteristic absorption spectrum information in the near-infrared region, be certain mathematical relation between spectral absorption intensity and component concentration, usually follow Beer law, because NIR spectral region information distributes comparatively complicated, this mathematical relation is different from typical curve, is commonly called mathematical model.By collecting some and representative standard model composition calibration set, determine its NIR spectrogram, use special Chemical Measurement software, between NIR spectrogram and component concentration, set up corresponding mathematical model.The employed standard model of near infrared modeling is the actual sample of measuring or calculated index components content or other character data through the traditional analysis method, but not pure standard items, mathematical model is the basis of realizing quantitative test.
The range of application of near infrared spectrometer is very extensive, can be used for outside the detection of raw material, intermediate, product, material situation of change in the real-time monitoring unit equipment, detecting data can be integrated with control system, form complete automatic control program, the data that real-time online detects can be transported to Central Control Room.
Summary of the invention
The object of the invention is to disclose a kind of assay method that utilizes paracetamol and moisture in the near infrared ray pharmaceutical composition.
The present invention seeks to be achieved by the following scheme:
Pharmaceutical composition bulk drug of the present invention consists of:
Pharmaceutical composition bulk drug composition of the present invention is preferably:
Pharmaceutical composition bulk drug composition of the present invention also is preferably:
Pharmaceutical composition bulk drug composition of the present invention also is preferably:
Preparation of drug combination method of the present invention comprises the steps:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae and mix and add respectively that the 4-6 volume is doubly measured, decocting boils 2 times, decocting time was respectively 1-3 hour, and collecting decoction filters, and filtrate is concentrated into 50 ℃, and to record relative density be 1.10g/ml, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, again with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle, dry, spray 75% peppermint oil ethanolic solution, mixing is made 1000 weight portions, namely get medicament composition granule of the present invention, be used for assay;
Preparation of drug combination method of the present invention preferably adopts following steps:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae and mix and add respectively that 5 volumes are doubly measured, decocting boils 2 times, decocting time was respectively 2 hours, and collecting decoction filters, and it is 1.10g/ml that filtrate concentrating records relative density, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, again with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle, dry, spray 75% peppermint oil ethanolic solution, mixing is made 1000 weight portions, namely get medicament composition granule of the present invention, be used for assay;
The detection method of pharmaceutical composition of the present invention comprises the steps:
(1) input of sample size: click " operation button " software of the near infrared spectrometer that disposes integrating sphere diffuse reflection module and the computer system function software interface that is equipped with it, prompting input sample size to be analyzed; Import sample size to be analyzed therein, click " affirmation " button;
(2) collected specimens spectrum: instrument is finished the background collection of sample automatically, after the background collection finishes, is ready to sample on request, clicks that " " button namely begins collected specimens spectrum to continue operation;
(3) output of sampling report: after the sample spectra collection finishes, workflow will be called the content that " Quantitative Analysis Model " measures paracetamol and moisture automatically, and obtain report, and the measurement of a sample so far finishes.
The inventive method can also be imported next duplicate samples according to step (1), and the workflow of instrument can be got back to step (2) automatically, begins the analysis of next duplicate samples and obtains the report of this sample; Circulation is measured, and to all measured end of all samples, quits a program, and finishes the assay of paracetamol and moisture in a collection of pharmaceutical composition of the present invention.
Wherein, the Quantitative Analysis Model of Paracetamol and moisture is set up by following method in the described pharmaceutical composition of the present invention:
Sample thief from 31 batches pharmaceutical composition of the present invention, get 20g for every batch, put into sample cup, for reducing the error that the sample unevenness is brought, when gathering, make the sample cup rotation, use is equipped with the near infrared spectrometer of integrating sphere diffuse reflection module to gather spectrum, and the near infrared primary light spectrogram of the pharmaceutical composition of the present invention that obtains is as accompanying drawing 1;
Adopt partial least square method (PLS) deal with data, and spectrogram is carried out single order differential and the level and smooth pre-service of Norris, obtain spectrogram after the pre-service, as accompanying drawing 2;
In the pharmaceutical composition of the present invention that will measure by chemical analysis method paracetamol and moisture to contain numerical quantity related with infrared spectrogram, the related algorithm of operation Chemical Measurement, after the optimization process, set up mathematical model, namely obtain the Quantitative Analysis Model of Paracetamol and moisture in the pharmaceutical composition of the present invention.
Wherein, the sample number of described circulation measurement can be one or more.
The pass of weight portion of the present invention and parts by volume is kg/L.
The present invention adopts near infrared spectrometer and disposes component content in the integrating sphere diffuse reflection module testing 999 board cold drug particles (embodiment 1 preparation) and measure the model that foundation is obtained to carry out the deviation of cross validation very little, and it is practicable having confirmed the employing near infrared spectrometer and having disposed in the integrating sphere diffuse reflection module testing 999 board cold drug particles that component content measures;
Near infrared spectrometer detects rapidly and efficiently, and each sample only needs seldom that the time just can obtain concentration value very accurately, and this is that classic method is incomparable; Use near infrared spectrometer, multiple index can be simultaneously determined, the mensuration of all indexs, the result can tabulate automatically and be presented in the summary report, tediously long, dull chemical assay just can become efficiently, simple, the analyst can be freed from the heavy duplication of labour, to drop into more energy to more valuable work; The near infrared assay method does not destroy sample, can online real-time testing, monitor the concentration change of each composition in the sample in real time; Near infrared spectrometer is in use without any consumables such as organic solvents, and the operation of instrument and maintenance cost are extremely low; Near infrared technology is described as the analytical technology of " green high-efficient ", does not therefore have the environmental pollution that organic solvent consumption brings; NIR technology is not owing to need sample pretreatment, the software of near-infrared analyzer can guarantee that operating personnel carry out shirtsleeve operation under the SOP of standard, and operating parameter can not be modified, and model also can be protected very safely.Following experimental example and embodiment further specify but are not limited to the present invention.
The foundation of experimental example 1 paracetamol mathematical model
(1) chemical analysis method carries out the paracetamol assay
Adopt the high effective liquid chromatography for measuring among second appendix VD of version pharmacopeia in 2010.
Chromatographic condition and system suitability test: be filling agent with octadecylsilane chemically bonded silica; Methanol-water (25: 75) is the phase that flows, and detects wavelength 245nm.Number of theoretical plate calculates by paracetamol should be not less than 4000.
The preparation of reference substance solution: precision takes by weighing 105 ℃ of paracetamol reference substances that are dried to constant weight and puts in right amount in the measuring bottle, is dissolved in water and is diluted to scale, shakes up, and is made into the solution that contains paracetamol 0.08mg among every 1ml.
The preparation of need testing solution: get pharmaceutical composition of the present invention, the mixing porphyrize, precision takes by weighing 1g, puts in the 250ml measuring bottle, adds the about 100ml of water, and ultrasonic concussion 5 minutes is put to room temperature, adds water to scale, shakes up, and 0.45 μ m miillpore filter filters, and gets the continuous liquid of considering, namely.
Determination method: precision is drawn reference substance solution and each 10 μ l of need testing solution respectively, injects liquid chromatograph, measures, namely.
The pharmaceutical composition of the present invention (999 board cold drug particle) of every 10g embodiment 1 preparation contains paracetamol (C
8H
9O
2N) should be 95.0%～105.0% of labelled amount.
The pharmaceutical composition of the present invention (999 board cold drug particle) of every 10g embodiment 1 preparation contains paracetamol 0.25g.
(2) foundation of paracetamol mathematical model:
In the pharmaceutical composition of the present invention (999 board cold drug particle) that chamber HPLC is by experiment measured paracetamol contain numerical quantity with the infrared spectrogram association, the related algorithm of operation Chemical Measurement after the optimization process, is set up the paracetamol mathematical model.
(3) the sample predicted value of the paracetamol mathematical model of Jian Liing and chemical method obtain between the lab analysis value relevant, obtain correlogram as shown in Figure 3, the related coefficient (Corr.Coeff.) that draws the model of foundation is 0.99945, and proofreading and correct mean square deviation (RMSEC) is 0.0636.
The foundation of experimental example 2 moisture mathematical models
(1) chemical analysis method carries out the mensuration to moisture,
Adopt the aquametry among first appendix IX of version pharmacopeia in 2010 H, first method (oven drying method)
Get in the middle of the pharmaceutical composition of the present invention (999 board cold drug particle) of embodiment 1 preparation two parts of the parallel samplings of product, each 2～3g puts in the good measuring cup of constant weight, weighs, and records numerical value; 105 ℃ of baking ovens, constant weight 6 hours cools and weighs, record numerical value;
Calculate:
Measuring cup constant weight: W
1Sampling amount: W
2Heavy after the sample constant weight: W
3
Pharmaceutical composition of the present invention (the 999 board cold drug particle) moisture of every 10g embodiment 1 preparation contains should be lower than 3% of sample size.
(2) foundation of moisture mathematical model:
By experiment in the pharmaceutical composition of the present invention (999 board cold drug particle) of embodiment 1 preparation measured of chamber oven drying method moisture contain numerical quantity with the infrared spectrogram association, the related algorithm of operation Chemical Measurement through after the optimization process, is set up mathematical model.
(3) the sample predicted value of the moisture mathematical model of Jian Liing and chemical method obtain between the lab analysis value relevant, obtain correlogram as shown in Figure 4, the related coefficient (Corr.Coeff.) that draws the model of foundation is 0.99857, and proofreading and correct mean square deviation (RMSEC) is 0.00734.
Experimental example 3 cross validations
According to experimental example 1 and 2 mathematical models of setting up, adopt and stay a cross validation method to come evaluation model.Specific practice is therefrom to take out 1 interim verification sample of conduct at every turn, carries out modeling with remaining sample, then this 1 sample is predicted, so follows badly, obtains the intersection predicted value of each sample.
Table 1 paracetamol cross validation result
Show that from paracetamol cross validation result the cross validation maximum deviation is 2.74%, minimum deflection is 0.01%, and mean deviation is 1.05%, and deviation is less.
Table 2 moisture cross validation result
Moisture checking result shows that the cross validation maximum deviation is 9.16%, and minimum deflection is 0.01%, and mean deviation is 3.80%, and deviation is less.
Conclusion: adopt near infrared spectrometer and dispose component content in the pharmaceutical composition of the present invention (999 board cold drug particle) of integrating sphere diffuse reflection module testing embodiment 1 preparation and measure the model that foundation is obtained to carry out the deviation of cross validation very little, prove that component content mensuration is practicable in the pharmaceutical composition of the present invention (999 board cold drug particle) that adopts near infrared spectrometer and dispose integrating sphere diffuse reflection module testing embodiment 1 preparation.
Description of drawings
Fig. 1: pharmaceutical composition of the present invention (999 board cold drug particle) near infrared primary light spectrogram
Fig. 2: the pharmaceutical composition of the present invention after single order differential and the Norris smoothing processing (999 board cold drug particle) near infrared light spectrogram
Fig. 3: the correlogram between modeling sample predicted value and the paracetamol assay value and residual error distribution plan
Fig. 4: the correlogram between modeling sample predicted value and the water analysis value and residual error distribution plan
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment
Embodiment 1:
Pharmaceutical composition of the present invention is to prepare by the following method:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae and mix and add 5 liters, decocting respectively and boil 2 times, decocting time was respectively 2 hours, and collecting decoction filters, and it is 1.10g/ml that filtrate concentrating records relative density, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, again with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle, dry, spray 75% peppermint oil ethanolic solution, mixing is made 1000 kilograms, namely get medicament composition granule of the present invention, be used for assay;
The method of pharmaceutical composition assay of the present invention comprises the steps:
(1) preparation of test macro: near infrared spectrometer and the computer of opening configuration integrating sphere diffuse reflection module, preheating 2 hours, it is 60% with humidity that the temperature of record operating environment is 20 ℃, analysis process " pharmaceutical composition (999 board cold drug particle) particle detection " is selected by the start-up system function software from the system operating software interface.
(2) preparation of sample before the mensuration: clean sample rotating cup inside surface and hot spot window with hairbrush and lens wiping paper, 20g cold drug particulate samples is packed in the sample rotating cup, the light sample surfaces of pressing, guarantee sample homogeneity to greatest extent, clean the sample cup bottom with lens wiping paper or hairbrush, the sample cup that installs sample is placed on the spinner support, prepare to measure.
(3) input of sample size: click the operation button software at system operating software interface, eject the sample measurement window, prompting input sample size to be analyzed.Import 20 kilograms of sample sizes to be analyzed therein, click ACK button.
(4) collected specimens spectrum: instrument is finished the background collection of sample automatically, and the background collection is carried out the sample spectra collection after finishing.(2) are ready to sample set by step, click the continuation action button, namely begin collected specimens spectrum.
(5) output of sampling report: after the sample spectra collection finishes, workflow will be called Quantitative Analysis Model automatically, and to measure paracetamol be that the content of 99.8% and moisture of expression amount is 2.8% of example weight, and obtain report, carry out the measurement of next sample.
(6) preparation of next duplicate samples is measured, according to step (2), (3) prepare next duplicate samples, the workflow of instrument can be got back to step (4) automatically, begin the analysis of next duplicate samples, sampling report output result, the content of paracetamol is 100.9% of labelled amount, the content of moisture is for being 2.6% of example weight.Quit a program, the assay of paracetamol and moisture finishes in this batch pharmaceutical composition (999 board cold drug particle).
Embodiment 2:
Pharmaceutical composition of the present invention is to prepare by the following method:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae and mix and add 5 liters, decocting respectively and boil 2 times, decocting time was respectively 2 hours, and collecting decoction filters, and it is 1.10g/ml that filtrate concentrating records relative density, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, again with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle, dry, spray 75% peppermint oil ethanolic solution, mixing is made 1000 kilograms, namely get medicament composition granule of the present invention, be used for assay;
(1) preparation of test macro: near infrared spectrometer and the computer of opening configuration integrating sphere diffuse reflection module, preheating 3 hours, it is 40% with humidity that the temperature of record operating environment is 18 ℃, analysis process " pharmaceutical composition (999 board cold drug particle) particle detection " is selected by the start-up system function software from the system operating software interface.
(2) preparation of sample before the mensuration: clean sample rotating cup inside surface and hot spot window with hairbrush and lens wiping paper, 20g cold drug particulate samples is packed in the sample rotating cup, the light sample surfaces of pressing, guarantee sample homogeneity to greatest extent, clean the sample cup bottom with lens wiping paper or hairbrush, the sample cup that installs sample is placed on the spinner support, prepare to measure.
(3) input of sample size: click the operation button software at system operating software interface, eject the sample measurement window, prompting input sample size to be analyzed.Import 20 kilograms of sample sizes to be analyzed therein, click ACK button.
(4) collected specimens spectrum: instrument is finished the background collection of sample automatically, and the background collection is carried out the sample spectra collection after finishing.(2) are ready to sample set by step, click the continuation action button, namely begin collected specimens spectrum.
(5) output of sampling report: after the sample spectra collection finishes, workflow will be called Quantitative Analysis Model automatically, and to measure paracetamol be that the content of 99.7% and moisture of labelled amount is for being 1.6% of example weight, and obtain report, carry out the measurement of next sample.
(6) preparation of next duplicate samples is measured, according to step (2), (3) prepare next duplicate samples, the workflow of instrument can be got back to step (4) automatically, begin the analysis of next duplicate samples, sampling report output result, the content of paracetamol is 100.7% of labelled amount, the content of moisture is 1.2% of example weight.
(7) continuous coverage: according to step (6), circulation is carried out, and obtaining sampling report output result respectively is 102.3% of labelled amount for paracetamol, and the content of moisture is 1.5%, obtains above-mentioned measurement result and meets drug standards regulation.
(8) continuous coverage: according to step (6), circulation is carried out, and obtaining sampling report output result respectively is 101.3% of labelled amount for the content of paracetamol, and the content of moisture is 2.9% of example weight, obtain above-mentioned measurement result, after judge whether to meet drug standards regulations.Quit a program, the assay of paracetamol and moisture finishes in this batch pharmaceutical composition (999 board cold drug particle).
Embodiment 3:
Pharmaceutical composition of the present invention is to prepare by the following method:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae and mix and add 5 liters, decocting respectively and boil 2 times, decocting time was respectively 2 hours, and collecting decoction filters, and it is 1.10g/ml that filtrate concentrating records relative density, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, again with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle, dry, spray 75% peppermint oil ethanolic solution, mixing is made 1000 kilograms, namely get medicament composition granule of the present invention, be used for assay;
(1) preparation of test macro: near infrared spectrometer and the computer of opening configuration integrating sphere diffuse reflection module, preheating 3 hours, it is 30% with humidity that the temperature of record operating environment is 23 ℃, analysis process " pharmaceutical composition (999 board cold drug particle) particle detection " is selected by the start-up system function software from the system operating software interface.
(2) preparation of sample before the mensuration: clean sample rotating cup inside surface and hot spot window with hairbrush and lens wiping paper, 20g cold drug particulate samples is packed in the sample rotating cup, the light sample surfaces of pressing, guarantee sample homogeneity to greatest extent, clean the sample cup bottom with lens wiping paper or hairbrush, the sample cup that installs sample is placed on the spinner support, prepare to measure.
(3) input of sample size: click the operation button software at system operating software interface, eject the sample measurement window, prompting input sample size to be analyzed.Import 20 kilograms of sample sizes to be analyzed therein, click ACK button.
(4) collected specimens spectrum: instrument is finished the background collection of sample automatically, and the background collection is carried out the sample spectra collection after finishing.(2) are ready to sample set by step, click the continuation action button, namely begin collected specimens spectrum.
(5) output of sampling report: after the sample spectra collection finished, workflow will be called Quantitative Analysis Model automatically, and to measure paracetamol be that the content of 99.2% and moisture of labelled amount is 1.8%, and obtain report, carries out the measurement of next sample.
(6) preparation of next duplicate samples is measured, according to step (2), (3) prepare next duplicate samples, the workflow of instrument can be got back to step (4) automatically, begin the analysis of next duplicate samples, sampling report output result, the content of paracetamol is 101.6% of labelled amount, the content of moisture is 2.2%.
(7) continuous coverage: according to step (6), circulation is carried out, and obtains sampling report output result such as following table respectively:
| Paracetamol content (% of expression amount) | Moisture (% of testing sample amount) |
| 102.1％ | 1.5％ |
| 96.5％ | 0.9％ |
| 99.8％ | 2.3％ |
| 103.2％ | 1.2％ |
| 105.6％ | 1.6％ |
| 100.6％ | 1.5％ |
| 101.2％ | 1.9％ |
| 99.6％ | 2.8％ |
| 98.2％ | 3.2％ |
(8) according to above-mentioned measurement result, judge whether to meet drug standards regulation.Quit a program, the assay of paracetamol and moisture finishes in this batch pharmaceutical composition (999 board cold drug particle).
Claims (1)
1. a Determination on content method of utilizing paracetamol and moisture in the near infrared ray pharmaceutical composition is characterized in that comprising the steps:
(1) preparation of test macro: near infrared spectrometer and the computer of opening configuration integrating sphere diffuse reflection module, preheating 2 hours, it is 60% with humidity that the temperature of record operating environment is 20 ℃, analysis process " medicament composition granule detection " is selected by the start-up system function software from the system operating software interface;
(2) preparation of sample before the mensuration: clean sample rotating cup inside surface and hot spot window with hairbrush and lens wiping paper, 20g drug regimen matter sample is packed in the sample rotating cup, the light sample surfaces of pressing, guarantee sample homogeneity to greatest extent, clean the sample cup bottom with lens wiping paper or hairbrush, the sample cup that installs sample is placed on the spinner support, prepare to measure;
(3) input of sample size: click the operation button software at system operating software interface, eject the sample measurement window, prompting input sample size to be analyzed; Import sample size 20 grams to be analyzed therein, click ACK button;
(4) collected specimens spectrum: instrument is finished the background collection of sample automatically, and the background collection is carried out the sample spectra collection after finishing; (2) are ready to sample set by step, click the continuation action button, namely begin collected specimens spectrum;
(5) output of sampling report: after the sample spectra collection finishes, workflow will be called the content that Quantitative Analysis Model is measured paracetamol and moisture automatically, and obtain report, and the measurement of a sample so far finishes;
Wherein, the method for building up of the Quantitative Analysis Model of paracetamol and moisture is as follows in the described pharmaceutical composition:
Sample thief from 31 batches pharmaceutical composition, get 20g for every batch, put into sample cup, for reducing the error that the sample unevenness is brought, when gathering, make the sample cup rotation, use is equipped with the near infrared spectrometer of integrating sphere diffuse reflection module to gather spectrum, the near infrared primary light spectrogram of the pharmaceutical composition that obtains;
Adopt the partial least square method deal with data, and spectrogram is carried out single order differential and the level and smooth pre-service of Norris, obtain spectrogram after the pre-service;
In the pharmaceutical composition that will measure by chemical analysis method paracetamol and moisture to contain numerical quantity related with infrared spectrogram, the related algorithm of operation Chemical Measurement, after the optimization process, set up mathematical model, namely obtain the Quantitative Analysis Model of paracetamol and moisture in the pharmaceutical composition;
Wherein, the foundation of paracetamol Quantitative Analysis Model:
(1) chemical analysis method carries out the paracetamol assay
Adopt the high effective liquid chromatography for measuring among second appendix VD of version pharmacopeia in 2010;
Chromatographic condition and system suitability test: be filling agent with octadecylsilane chemically bonded silica; Ratio is that 25: 75 methanol-water is the phase that flows, and detects wavelength 245nm, and number of theoretical plate calculates by paracetamol should be not less than 4000;
The preparation of reference substance solution: precision takes by weighing 105 ℃ of paracetamol reference substances that are dried to constant weight and puts in right amount in the measuring bottle, is dissolved in water and is diluted to scale, shakes up, and is made into the solution that contains paracetamol 0.08mg among every 1ml;
The preparation of need testing solution: the compositions of getting it filled, the mixing porphyrize, precision takes by weighing 1g, puts in the 250ml measuring bottle, adds the about 100ml of water, and ultrasonic concussion 5 minutes is put to room temperature, adds water to scale, shakes up, and 0.45 μ m miillpore filter filters, and gets subsequent filtrate, namely;
Determination method: precision is drawn reference substance solution and each 10 μ l of need testing solution respectively, injects liquid chromatograph, measures, namely;
(2) foundation of paracetamol mathematical model
In the pharmaceutical composition that chamber HPLC is by experiment measured paracetamol contain numerical quantity with the infrared spectrogram association, the related algorithm of operation Chemical Measurement after the optimization process, is set up the paracetamol mathematical model;
(3) the sample predicted value of the paracetamol mathematical model of Jian Liing and chemical method obtain between the lab analysis value relevantly, obtain correlogram, the related coefficient that draws the model of foundation is 0.99945, proofreading and correct mean square deviation is 0.0636;
Wherein, the foundation of water and basis weight analytical model:
(1) chemical analysis method carries out the mensuration of moisture
Adopt the aquametry among first appendix IX of version pharmacopeia in 2010 H, oven drying method;
Two parts of the parallel samplings of product of getting it filled in the middle of the compositions, each 2～3g puts in the good measuring cup of constant weight, weighs, and records numerical value; 105 ℃ of baking ovens, constant weight 6 hours cools and weighs, record numerical value; Calculate:
Moisture (%)=[(W
1+ W
2-W
3)/W
2] * 100%;
Measuring cup constant weight: W
1Sampling amount: W
2Heavy after the sample constant weight: W
3
Every 10g pharmaceutical composition moisture contains should be lower than 3% of sample size;
(2) foundation of moisture mathematical model:
By experiment in the pharmaceutical composition measured of chamber oven drying method moisture contain numerical quantity with the infrared spectrogram association, the related algorithm of operation Chemical Measurement through after the optimization process, is set up mathematical model;
(3) relevant between the sample predicted value of the moisture mathematical model of Jian Liing and the lab analysis value that chemical method obtains, obtain correlogram, the related coefficient that draws the model of foundation is 0.99857, proofreading and correct mean square deviation is 0.00734;
The bulk drug of described pharmaceutical composition consists of:
20 kilograms of 491 kilograms of paracetamol of evodia lepta
0.4 kilogram of 327 kilograms of caffeine of railway beggarticks herb
0.4 kilogram of 246 kilograms of chlorphenamine maleate of mother chrysanthemum
0.2 liter of 736 kilograms of peppermint oil of Flos Ilicis Asprellae
Described pharmaceutical composition is to prepare by the following method:
(1) get bulk drug evodia lepta, railway beggarticks herb, mother chrysanthemum and Flos Ilicis Asprellae mixing and add 5 premium on currency decoction 2 times respectively, decocting time was respectively 2 hours, and collecting decoction filters, and it is 1.10g/ml that filtrate concentrating records relative density, gets concentrate;
(2) concentrate is put be chilled to room temperature and add ethanol, make concentration of alcohol reach 50%-80%, leave standstill, filter, be concentrated into thick paste after reclaiming ethanol;
(3) paracetamol fine powder and cane sugar powder are added in step (2) thick paste, with the saturated aqueous solution mixing of chlorphenamine maleate and caffeine, make particle again, drying is sprayed 75% peppermint oil ethanolic solution, mixing, make 1000 kilograms, namely get described pharmaceutical composition.
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| CN104833654A (en) * | 2015-05-13 | 2015-08-12 | 华润三九医药股份有限公司 | Method and application for rapidly detecting mother chrysanthemum medicinal materials by utilizing near infrared spectroscopy |
| CN105353063B (en) * | 2015-12-07 | 2018-04-24 | 华润三九（郴州）制药有限公司 | Compound cold drug stream livering ingredient standard finger-print and construction method, application |
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