CN104597171A - High performance liquid chromatography analysis method of acarbose and its preparation - Google Patents
High performance liquid chromatography analysis method of acarbose and its preparation Download PDFInfo
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Abstract
The invention belongs to the field of a novel drug technology, relates to an analysis determination method of a drug acarbose for treating insulin dependent-type or independent-type diabetes and its preparation, and concretely relates to a high performance liquid chromatography analysis method of acarbose and its preparation. Aiming at solving the problems of the existing acarbose detection, the invention provides the analysis determination method of acarbose and its preparation and the method has good stability, good reappearance and simple processes. The method utilizes in-series combination of high performance liquid chromatography separation and UV detection to realize analysis detection of acarbose and its preparation. The method utilizes an amino silane bonded silica gel chromatographic column as a stationary phase and an acetonitrile-phosphate solution as a mobile phase. The convenient and fast high performance liquid chromatography analysis method is used for detection of related substances and content of acarbose and its preparation, has good repeatability, accuracy and stability, has stable acarbose main peak retention time and is conducive to drug quality control.
Description
Technical field
The invention belongs to medicine new technical field, relate to a kind of medicine acarbose and analysis of pharmaceutical dosage forms assay method thereof for the treatment of insulin-dependent or non-insulin dependent diabetes, the HPLC analytical method of acarbose and preparation thereof specifically.
Background technology
According to bibliographical information and the national drug standards, mensuration acarbose and preparation thereof adopt high efficient liquid phase analysis method to have:
1, the acarbose content method that records of the national drug standards
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2000 two annex V D).
Chromatographic condition and system suitability test amino chemically bonded silica are filling agent; Acetonitrile-phosphate buffer (70:30) is mobile phase; Flow velocity is 2ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Take 20mg acarbose reference substance appropriate, the solution containing 1mg in every 1ml is made by water Under Ultrasonic Vibration thixotropy solution, getting above-mentioned solution 25ml puts in 50ml measuring bottle, with 0.1mol/L sodium hydroxide solution 1ml, shake up, after room temperature places 8 hours, with 0.1mol/L hydrochloric acid solution 1ml, add water to scale as system suitability solution.Get this liquid 10 μ l, injection liquid chromatography, record chromatogram, acarbose peak and the peak-to-peak degree of separation of its catabolite must not be less than 1.3, and peak sequence is acarbose alkaline degradation product peak and acarbose peak.
Determination method precision takes this product and is about 10mg, puts in 10ml measuring bottle, is dissolved in water and is diluted to scale, shake up, and precision measures 10 μ l injection liquid chromatographies, record chromatogram; Separately get acarbose reference substance appropriate, be measured in the same method, by external standard method with calculated by peak area, obtain final product.
2, the acarbose related substance method recorded of the national drug standards
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2000 two annex V D).
Chromatographic condition and system suitability test amino chemically bonded silica are filling agent; Acetonitrile-phosphate buffer (70:30) is mobile phase; Flow velocity is 2ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Take 20mg acarbose reference substance appropriate, the solution containing 1mg in every 1ml is made by water Under Ultrasonic Vibration thixotropy solution, getting above-mentioned solution 25ml puts in 50ml measuring bottle, with 0.1mol/L sodium hydroxide solution 1ml, shake up, after room temperature places 8 hours, with 0.1mol/L hydrochloric acid solution 1ml, add water to scale as system suitability solution.Get this liquid 10 μ l, injection liquid chromatography, record chromatogram, acarbose peak and the peak-to-peak degree of separation of its catabolite must not be less than 1.3, and peak sequence is acarbose alkaline degradation product peak and acarbose peak.
It is appropriate, accurately weighed that determination method gets this product, and add water the solution made containing 1mg in every 1ml, as need testing solution.It is appropriate that precision measures need testing solution, and thin up becomes the solution solution in contrast containing 0.04mg in every 1ml.Get contrast solution 20 μ l injection liquid chromatography, regulate detection sensitivity, the peak height of main composition chromatographic peak is made to be about 10% ~ 15% of registering instrument full scale, precision measures need testing solution and each 20 μ l of contrast solution again, injection liquid chromatography respectively, record chromatogram is to 2 times of main composition peak retention time.As aobvious impurity peaks in need testing solution chromatogram, each impurity area and the main composition peak area of contrast solution must not be greater than, single impurity peak area must not be greater than 3/8 of the main composition peak area of contrast solution.
3, the acarbose tablet content method that records of the national drug standards
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2000 two annex V D).
Chromatographic condition and system suitability test amino chemically bonded silica are filling agent; Acetonitrile-phosphate buffer (70:30) is mobile phase; Flow velocity is 2ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Theoretical cam curve must not lower than 2500 by acarbose peak, and component A relative retention time is 0.9, should be separated completely with main peak, and the retention time at acarbose peak is about 11 ~ 18 minutes.
Determination method gets this product 20, accurately weighed, porphyrize, precision takes fine powder appropriate (being about equivalent to acarbose 250mg), put in 25ml measuring bottle, add water about 15ml, and ultrasonic process 10 minutes, is diluted with water to scale, shake up, filter with filter membrane, get subsequent filtrate 10 μ l injection liquid chromatography, record chromatogram; Separately get acarbose reference substance appropriate, be measured in the same method, by external standard method with calculated by peak area.
4, the acarbose tablet related substance method recorded of the national drug standards
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2000 two annex V D).
Chromatographic condition and system suitability test amino chemically bonded silica are filling agent; Acetonitrile-phosphate buffer (70:30) is mobile phase; Flow velocity is 2ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Theoretical cam curve must not lower than 2500 by acarbose peak, and component A relative retention time is 0.9, should be separated completely with main peak, and the retention time at acarbose peak is about 11 ~ 18 minutes.
Determination method gets need testing solution under assay item as need testing solution.Another precision measures need testing solution 1ml, puts in 100ml measuring bottle, is diluted with water to scale, in contrast solution.Get contrast solution 10 μ l injection liquid chromatography, regulate detection sensitivity, make the peak height of main composition chromatographic peak be about 25% of registering instrument full scale, then precision measures need testing solution and each 10 μ l of contrast solution, injection liquid chromatography respectively, record chromatogram is to 2 times of main composition peak retention time.
The relative retention time of known side components 2, B, A, C, 4A, 4B, 4C is respectively 0.5,0.8,0.9,1.2,1.8,2.0,2.3.Other single unknown impuritie peak areas except main composition and above accessory substance must not be greater than 1/2 of the main composition peak area of contrast solution.Unknown impuritie peak area sum must not be greater than the main composition peak area of contrast solution, and the peak area of known accessory substance A must not be greater than 1.2 times of the main composition peak area of contrast solution.
5, the acarbose related substance method recorded of European Pharmacopoeia, American Pharmacopeia and British Pharmacopoeia
Chromatographic condition and system suitability test amino silane key and silica gel are filling agent (5 μm, 4.0mm × 250mm) chromatographic column, column temperature 35 DEG C, mobile phase: acetonitrile-phosphate buffer (gets potassium dihydrogen phosphate 0.60g, disodium phosphate dihydrate 0.35g, adds 1000ml water and makes dissolving) (75:25).Flow velocity is 2.0ml/min,
Determined wavelength is 210nm.Sample size is 10 μ l, and record chromatogram is to 2.5 times of acarbose main peak retention time.
Precision takes the water-soluble solution that 0.200g acarbose spends carbon dioxide, and is diluted to 10ml as need testing solution; Water-soluble solution 1 bottle of acarbose CRS solution (a) in contrast of carbon dioxide is removed with 5ml; Take 20mg acarbose peak and differentiate reference substance (impure A, B, C, D, E, F, H, G), remove the water-soluble solution solution (b) in contrast of carbon dioxide with 1ml; Measure 1.0ml need testing solution, the water spending carbon dioxide is diluted to 100ml solution (c) in contrast.In contrast solution (b) chromatogram, the peak valley ratio that the peak height of impurity A and impurity A and main peak are shown in is not less than 1.2.
The analytical approach of above related substance and content, the pH value of mobile phase shows alkalescent, and nh 2 column acarbose main peak retention time used is unstable, drifts about backward gradually.For solving the problem of acarbose main peak drift, after us, find out the analytical approach of a set of applicable acarbose and preparation related substances and assay.The method is fast and convenient, and precision is high, good stability, and result is accurate, and replica test and content recovery test RSD are all less than 2.0%, and limit of identification (s/n=3) is 0.40ng/ml.
Summary of the invention
The object of the invention is to provide a kind of good stability, favorable reproducibility, simple to operate, for the analysis determining method of acarbose and preparation thereof.
The present invention solves the problems of the technologies described above taked technical scheme: this method adopts the be separated mode of connecting with UV detect of high-efficient liquid to carry out analysis to acarbose and preparation thereof and detect; The water-soluble solution of acarbose and preparation thereof to be diluted in every 1ml containing the solution of acarbose 0.5mg ~ 50mg as need testing solution, sampling volume 1 ~ 100 μ l, adopt Stationary liquid amino chemically bonded silica chromatographic column, mobile phase is acetonitrile-phosphate solution, volume ratio scope containing acetonitrile in wherein said mobile phase is 50% ~ 90%, the volume ratio scope of phosphate-containing solution is 10% ~ 50%, and flow rate of mobile phase is 0.5 ~ 3.0ml/min; UV detect wavelength 200nm ~ 230nm, measures the related substance of acarbose and preparation thereof and content.
Further, the mobile phase pH value that we have chance with described is 2.5 ~ 7.2, and optimal pH is 6.8.
Further, we disclose described phosphate solution to be made up of one or more in phosphoric acid solution, potassium dihydrogen phosphate, disodium phosphate soln, sodium dihydrogen phosphate, dipotassium hydrogen phosphate solution, sodium radio-phosphate,P-32 solution, potassium phosphate solution.
Simultaneously, we further disclose the concrete composition of phosphate solution, described phosphate solution is the mixed liquor of potassium dihydrogen phosphate, disodium phosphate soln and phosphoric acid solution, and wherein potassium dihydrogen phosphate mass body volume concentrations is 0.01% ~ 10%, and the best is 0.04 ~ 1%; Sodium hydrogen phosphate mass body volume concentrations is 0.01% ~ 10%, and the best is 0.01 ~ 1%; Phosphoric acid solution is as mobile phase pH value regulator, and phosphoric acid quality volumetric concentration is 0.1% ~ 95%, and the best is 10% ~ 50%.
In the proportioning of mobile phase, we are preferred further, and in described mobile phase, volume the best of acetonitrile is 65% ~ 80%; Volume the best of described phosphate solution is 20% ~ 35%.
Finally, we further disclose preferably testing conditions be UV detect wavelength is 210nm, and need testing solution is 20mg/ml containing acarbose, and sampling volume is 10 μ l, and flow rate of mobile phase is 2ml/min.
The invention has the beneficial effects as follows: the present invention utilizes conveniently high performance liquid chromatography, the related substance of acarbose and preparation and content are detected, repeatability, accuracy and stability are all very good, particularly acarbose main peak retention time is stablized, and is conducive to the quality control of medicine.
Embodiment
Instrument: waters high performance liquid chromatograph, conventional supporting UV-detector.
Reagent: potassium dihydrogen phosphate (analyzing pure), acetonitrile (chromatographically pure), sodium hydrogen phosphate (analyzing pure), 10% phosphoric acid
Chromatographic column: amino chemically bonded silica chromatographic column
Determined wavelength: 210nm
Following examples illustrate the present invention, but do not limit the present invention in any way.
Embodiment 1: related substance
Chromatographic condition and system suitability amino chemically bonded silica are filling agent; Mixture of acetonitrile-phosphate buffer (25: 75), adjusts pH to 6.8 to be mobile phase with 10% phosphoric acid; Flow velocity is 2 ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Take 20mg acarbose impurity reference substance (impure A, B, C, D, E, F, G, H), 1 ml that adds water makes it dissolve, as system suitability solution.The peak height of impurity A and the high ratio of itself and the peak-to-peak peak valley of acarbose master must not be less than 1.2, press acarbose peak must not calculate lower than 2500 with theoretical cam curve.
Determination method gets this product, is dissolved in water and dilutes the solution made containing acarbose 20mg in every 1ml, as need testing solution; Precision measures 1ml, puts in 100ml measuring bottle, is diluted with water to scale, shake up, in contrast solution.Get contrast solution 10 μ l injection liquid chromatography, regulate detection sensitivity, make the peak height of major component chromatographic peak be about 25% of full scale; Measure each 10 μ l of system suitability solution, need testing solution and contrast solution injection liquid chromatography respectively respectively, record chromatogram is to 2.5 times of main composition peak retention time.The relative retention time of known impurities D, H, B, A, C, E, F, G is respectively 0.5,0.6,0.8,0.9,1.2,1.7,1.9,2.2.Peak area except known impurities A must not be greater than except 1.2 times (1.2%) of contrast solution main peak area, other single impurity peak area must not be greater than 0.5 times (0.5%) of contrast solution main peak area, each impurity peak area and contrast solution main peak area 4 times (4.0%) must not be greater than.
Embodiment 2: assay
Chromatographic condition and system suitability amino chemically bonded silica are filling agent; Mixture of acetonitrile-phosphate buffer (25: 75), adjusts pH to 6.8 to be mobile phase with 10% phosphoric acid; Flow velocity is 2 ml/min; Column temperature 35 DEG C, determined wavelength is 210nm.Take 20mg acarbose impurity reference substance (impure A, B, C, D, E, F, G, H), 1 ml that adds water makes it dissolve, as system suitability solution.The peak height of impurity A and the high ratio of itself and the peak-to-peak peak valley of acarbose master must not be less than 1.2, press acarbose peak must not calculate lower than 2500 with theoretical cam curve.
Determination method gets this product, accurately weighed, porphyrize, precision takes fine powder appropriate (being about equivalent to acarbose 500 mg), put in 25 ml measuring bottles, add water about 15 ml, ultrasonic process 10 min, let cool, be diluted with water to scale, shake up, filter, get subsequent filtrate 10 μ l injection liquid chromatography, record chromatogram.Separately get acarbose reference substance appropriate, be dissolved in water and make every 1ml about containing the solution of acarbose 20mg, product solution, is measured in the same method in contrast, by external standard method with calculated by peak area.
Claims (6)
1. the HPLC analytical method of acarbose and preparation thereof, is characterized in that: this method adopts the be separated mode of connecting with UV detect of high-efficient liquid to carry out analysis to acarbose and preparation thereof and detect; The water-soluble solution of acarbose and preparation thereof to be diluted in every 1ml containing the solution of acarbose 0.5mg ~ 50mg as need testing solution, sampling volume 1 ~ 100 μ l, adopt Stationary liquid amino chemically bonded silica chromatographic column, mobile phase is acetonitrile-phosphate solution, volume ratio scope containing acetonitrile in wherein said mobile phase is 50% ~ 90%, the volume ratio scope of phosphate-containing solution is 10% ~ 50%, and flow rate of mobile phase is 0.5 ~ 3.0ml/min; UV detect wavelength 200nm ~ 230nm, measures the related substance of acarbose and preparation thereof and content.
2. the HPLC analytical method of acarbose according to claim 1 and preparation thereof, is characterized in that: described mobile phase pH value is 2.5 ~ 7.2, and optimal pH is 6.8.
3. the HPLC analytical method of acarbose according to claim 1 and preparation thereof, is characterized in that: described phosphate solution is made up of one or more in phosphoric acid solution, potassium dihydrogen phosphate, disodium phosphate soln, sodium dihydrogen phosphate, dipotassium hydrogen phosphate solution, sodium radio-phosphate,P-32 solution, potassium phosphate solution.
4. the HPLC analytical method of acarbose according to claim 1 and preparation thereof, it is characterized in that: described phosphate solution is the mixed liquor of potassium dihydrogen phosphate, disodium phosphate soln and phosphoric acid solution, wherein potassium dihydrogen phosphate mass body volume concentrations is 0.01% ~ 10%, and the best is 0.04 ~ 1%; Sodium hydrogen phosphate mass body volume concentrations is 0.01% ~ 10%, and the best is 0.01 ~ 1%; Phosphoric acid solution is as mobile phase pH value regulator, and phosphoric acid quality volumetric concentration is 0.1% ~ 95%, and the best is 10% ~ 50%.
5. the HPLC analytical method of acarbose according to claim 1 and preparation thereof, is characterized in that: in described mobile phase, volume the best of acetonitrile is 65% ~ 80%; Volume the best of described phosphate solution is 20% ~ 35%.
6. the HPLC analytical method of acarbose according to claim 1 and preparation thereof, is characterized in that: UV detect wavelength is 210nm, and need testing solution is 20mg/ml containing acarbose, and sampling volume is 10 μ l, and flow rate of mobile phase is 2ml/min.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105572267A (en) * | 2016-03-14 | 2016-05-11 | 烟台大学 | Method for detecting acarbose through high performance liquid chromatography |
| CN106872635A (en) * | 2017-03-22 | 2017-06-20 | 江南大学 | A kind of method that chromatography of ions detects acarbose |
| CN111122724A (en) * | 2019-12-17 | 2020-05-08 | 纳谱分析技术（苏州）有限公司 | Method for analyzing acarbose and related substances |
| CN112305129A (en) * | 2020-11-24 | 2021-02-02 | 上海化工研究院有限公司 | Method for detecting residual content of acarbose in mushroom dregs |
| CN113670680A (en) * | 2021-06-30 | 2021-11-19 | 杭州中美华东制药江东有限公司 | Preparation method of acarbose impurity reference substance |
| CN114839299A (en) * | 2022-06-14 | 2022-08-02 | 哈药集团技术中心 | Disaccharide compound analysis method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105572267A (en) * | 2016-03-14 | 2016-05-11 | 烟台大学 | Method for detecting acarbose through high performance liquid chromatography |
| CN106872635A (en) * | 2017-03-22 | 2017-06-20 | 江南大学 | A kind of method that chromatography of ions detects acarbose |
| CN111122724A (en) * | 2019-12-17 | 2020-05-08 | 纳谱分析技术（苏州）有限公司 | Method for analyzing acarbose and related substances |
| CN111122724B (en) * | 2019-12-17 | 2022-08-30 | 纳谱分析技术（苏州）有限公司 | Method for analyzing acarbose and related substances |
| CN112305129A (en) * | 2020-11-24 | 2021-02-02 | 上海化工研究院有限公司 | Method for detecting residual content of acarbose in mushroom dregs |
| CN113670680A (en) * | 2021-06-30 | 2021-11-19 | 杭州中美华东制药江东有限公司 | Preparation method of acarbose impurity reference substance |
| CN114839299A (en) * | 2022-06-14 | 2022-08-02 | 哈药集团技术中心 | Disaccharide compound analysis method |
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