CN100348974C - Pharmaceutical composition detection method - Google Patents
Pharmaceutical composition detection method Download PDFInfo
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- CN100348974C CN100348974C CNB031544851A CN03154485A CN100348974C CN 100348974 C CN100348974 C CN 100348974C CN B031544851 A CNB031544851 A CN B031544851A CN 03154485 A CN03154485 A CN 03154485A CN 100348974 C CN100348974 C CN 100348974C
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- paracetamol
- pamabrom
- antergan
- maleic acid
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Abstract
The present invention relates to a detecting method for a medical composition, which can detect the content of three components simultaneously. A high-efficiency liquid chromatography is adopted, and a mixed solvent of a water phase with a proper pH value and an organic phase is used as a mobile phase for separating detection. The detecting method has the advantages of strong specificity and good separating effect, and the test process can be greatly simplified.
Description
Technical field
What the present invention relates to is a kind of method of quality control for the treatment of the compound medicine of premenstrual syndrome.It specifically is the method that detects three kinds of contained principal ingredient paracetamol, Pamabrom (Pamabrom) and maleic acid neo-antergan (Pyrilamine Maleate) content with high performance liquid chromatography simultaneously.
Technical background
It is premenstrual syndrome (PMS) that the composition that contains paracetamol, Pamabrom and maleic acid neo-antergan can be used for aspects such as a series of spirit, behavior and physique appear in the women of child-bearing age repeatedly before menstruation symptom, when control contains the drug quality of these three kinds of compositions, need accurately to measure the content of three kinds of compositions, still do not have the bibliographical information of relevant its assay method at present.
Paracetamol is NSAID (non-steroidal anti-inflammatory drug) commonly used, and the content assaying method of bibliographical information is more, and analytical approach has volumetric analysis, ultraviolet spectrophotometry and high performance liquid chromatography.Volumetric analysis need be from preparation extracts each component respectively to be measured, this method complex operation, time-consuming, and precision and accuracy are all relatively poor.Ultraviolet spectrophotometry also need be carried out the pre-treatment of sample, to get rid of the phase mutual interference between each component.
Bibliographical information adopts the condition of HPLC method mensuration paracetamol content also to have multiple at present.The chromatographic system that adopts mainly contains methanol-water, methyl alcohol-acetonitrile-water or methyl alcohol-acetonitrile-H
3PO
4Solution etc. are several." Chinese Pharmaceutical Journal " 2000,35 (11) second of the three ten-day periods of the hot season brilliance, Liu Meijuan " two component blood concentrations in the hplc simultaneous determination COMPOUND CHLORZOXAZONE TABLETS " literary composition in, adopt methanol-water (45: 55) to make the content that moving phase can be measured paracetamol; In " the HPLC method is measured 4 kinds of content of effective in the compound flu dispersing tablet " literary composition of Zhang Yuexin, adopt the cyano group post, methyl alcohol-acetonitrile-H in " PLA's Acta Pharmaceutica Sinica " 2000,16 (5)
3PO
4-triethanolamine (48: 26: 26: 0.25: 0.05) is made moving phase, can measure the content of paracetamol, pseudoephedrine, dextromethorphan, chlorphenamine simultaneously; " Mudanjiang Medical College's journal " 2001, in 22 (03) in " the HPLC method is measured the content of paracetamol in the vitamin C Yinqiao tablet " literary composition of ten thousand armies, Zhou Jinxia, adopt the C18 post, acetonitrile-methanol-water (10: 40: 50) is made moving phase, can be used for assay of paracetamol or the like.
Above-mentioned condition all be at paracetamol and with the analytical approach of other medicines composition, through test above-mentioned chromatographic condition to the present invention in the degree of separation of three kinds of components low, analysis time is long, all be not suitable for these three kinds of components contents and measure, also find no the detection method of measuring this three component simultaneously by retrieval.
Among the USP24-NF19 supplement2 under the pamabrom item chromatographic condition of theophylline inspection be water-methanol-glacial acetic acid (69: 30: 1), the chromatographic condition of related substance inspection is 0.01mol/L ammonium acetate-methyl alcohol-triethylamine (40: 60: 0.1) under the Pyrilamine Maleate item.Wherein a kind of assay of composition can only be used for through testing each chromatogram system, three kinds of components can not be measured simultaneously.
Measure the experimental study of carrying out at three kinds of components contents, we are surprised to find, when the mixed solvent that adopts water and organic phase, and the pH value scope of water is between 4.0～5.5 the time, three kinds of components all can better be separated, can use same system and in 30 minutes, measure three kinds of components contents simultaneously, simplify experimentation greatly, save a large amount of time and human and material resources cost.
Summary of the invention
The objective of the invention is to study a kind of easy and simple to handle, accuracy is high, favorable reproducibility, can measure the method that contains paracetamol, Pamabrom and maleic acid neo-antergan composition levels simultaneously.
Through a large amount of tests, we are surprised to find, and when the mixed solvent that adopts water and organic phase, and the pH value scope of water is 4.0～5.5 o'clock, and three kinds of components all can better be separated, accuracy height and favorable reproducibility.
The present invention adopts high performance liquid chromatography, is that moving phase is carried out separation determination with the water of specific pH and the mixed solvent of organic phase.Wherein water pH is preferably pH4.0-5.5, and more preferably 4.3-5.2 most preferably is 4.5-5.0.
In the moving phase system of the present invention, the water proportion is 40%-85%, preferred 50%-80%, more preferably 55%-75%.
No matter whether aqueous phase contains salt, as long as under specific pH condition, all can measure these three kinds of components contents simultaneously.Aqueous phase is preferably acetate and phosphate if contain salt, but and does not mean that to be these two kinds of salts.
In the moving phase system of the present invention, organic phase is lower alcohol or nitrile.Lower alcohol is preferably methyl alcohol, ethanol or isopropyl alcohol, and more preferably methyl alcohol or ethanol most preferably are methyl alcohol.Nitrile refers to acetonitrile.Organic phase can be single alcohol or nitrile, also can be their mixing.
Adopt the present invention can once measure the content of paracetamol in the pharmaceutical composition, Pamabrom and maleic acid neo-antergan simultaneously.The preparation formulation of this pharmaceutical composition is tablet, capsule or other pharmaceutically acceptable formulation.
In the chromatogram system of the present invention, sample only needs to get final product direct injected after the filtration with the moving phase dissolving, measures and once is no more than 30 minutes, and the theoretical plate number average of three kinds of component peaks is greater than 2000.This method precision height, good stability, the sample auxiliary material does not influence mensuration, and the recovery of high, medium and low concentration is all better, and reappearance is better, and method is easy and simple to handle, and is reliable and stable, practical, is suitable for very much this type of compound preparation production quality control.
Comparative Examples 1
Adopt high performance liquid chromatography, with octadecylsilane chemically bonded silica be filling agent (4.6 * 150mm), be moving phase with methanol-water (45: 55), flow velocity 1ml/min, detection wavelength 280nm.Sample thief (contains paracetamol 0.5mg/ml approximately, Pamabrom 0.025mg/ml, maleic acid neo-antergan 0.015mg/ml) 20ul injects liquid chromatograph, record chromatogram (Fig. 1), three kinds of compositions are effectively separated, regulate the different proportionings of methyl alcohol and water, three kinds of compositions all can not effectively be separated, and as seen simple methanol-water system can not be used for the separation of these three kinds of compositions.
Comparative Examples 2
With octadecylsilane chemically bonded silica be filling agent (4.6 * 150mm), be moving phase with acetonitrile-water (20: 80), flow velocity 1ml/min detects wavelength 280nm.Sample thief (containing paracetamol 0.5mg/ml approximately, Pamabrom 0.025mg/ml, maleic acid neo-antergan 0.015mg/ml) 20ul injects liquid chromatograph, the record chromatogram, and three kinds of compositions are effectively separated.Regulate the different proportionings of acetonitrile and water, three kinds of compositions all can not effectively be separated, and as seen simple acetonitrile-water system can not be used for the separation of these three kinds of compositions.
Comparative Examples 3
With octadecylsilane chemically bonded silica is filling agent, is moving phase with methyl alcohol-acetonitrile-water (is 3.9 with the vinegar acid for adjusting pH value) (48: 26: 26), and flow velocity 1ml/min detects wavelength 280nm.Sample thief (containing paracetamol 0.5mg/ml approximately, Pamabrom 0.025mg/ml, maleic acid neo-antergan 0.015mg/ml) 20ul injects liquid chromatograph, record chromatogram (Fig. 2), and three kinds of compositions are effectively separated.Regulate the different proportionings of methyl alcohol, acetonitrile and water, three kinds of compositions all can not effectively be separated, and the methyl alcohol of visible different proportionings, acetonitrile and adjusting pH value are that the combination of 3.9 water can not be used for separating of these three kinds of compositions.
Comparative Examples 4
With octadecylsilane chemically bonded silica is filling agent, is moving phase with methyl alcohol-0.005mol/L potassium phosphate solution (is 5.7 with the phosphorus acid for adjusting pH value) (30: 70), and flow velocity 1ml/min detects wavelength 280nm.Sample thief (containing paracetamol 0.5mg/ml approximately, Pamabrom 0.025mg/ml, maleic acid neo-antergan 0.015mg/ml) 20ul injects liquid chromatograph, the record chromatogram, and three kinds of compositions are effectively separated.Regulate the different proportionings of methyl alcohol, acetonitrile and water, three kinds of compositions all can not effectively be separated, and the methyl alcohol of visible different proportionings, acetonitrile and pH value are that the combination of 5.7 potassium phosphate solution can not be used for separating of these three kinds of compositions.
Embodiment 1
With octadecylsilane chemically bonded silica is that (4.6 * 150mm), so that 0.005mol/L ammonium acetate solution (is 4.6 with the acetic acid adjust pH)-methyl alcohol (50: 50) is moving phase, flow velocity 0.8ml/min detects wavelength 280nm to filling agent.Sample thief, the accurate title, decide (to be equivalent to paracetamol 500mg approximately, Pamabrom 25mg in right amount, maleic acid neo-antergan 15mg), puts in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, the record chromatogram is measured peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 99.70%, RSD=0.41%, and the Pamabrom recovery is 100.1%, RSD=0.47%, the maleic acid neo-antergan recovery is 100.0%, RSD=0.59%.
This three component of evidence is used said method can obtain good separation detection effect.
With eight alkyl silane bonded silica gels is that (4.6 * 150mm), so that 0.05mol/L ammonium acetate solution (containing triethylamine 0.05mol/L, is 4.9 with the acetic acid adjust pH)-methyl alcohol (70: 30) is moving phase, flow velocity ml/min detects wavelength 280nm to filling agent.Sample thief, the accurate title, decide (to be equivalent to paracetamol 500mg approximately, Pamabrom 25mg in right amount, maleic acid neo-antergan 15mg), puts in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, the record chromatogram is measured peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 99.70%, RSD=0.22%, and the Pamabrom recovery is 100.4%, RSD=0.64%, the maleic acid neo-antergan recovery is 99.89%, RSD=0.62%.
This three component of evidence is used said method can obtain good separation detection effect.
Embodiment 3
With octadecylsilane chemically bonded silica is filling agent, and so that water (is 5.3 with the acetic acid adjust pH)-methyl alcohol (70: 30) is moving phase, flow velocity 1ml/min detects wavelength 280nm.Sample thief, the accurate title, decide (to be equivalent to paracetamol 500mg approximately, Pamabrom 25mg in right amount, maleic acid neo-antergan 15mg), puts in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, the record chromatogram is measured peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 100.2%, RSD=0.44%, and the Pamabrom recovery is 99.8%, RSD=0.38%, the maleic acid neo-antergan recovery is 100.1%, RSD=0.37%.
This three component of evidence is used said method can obtain good separation detection effect.
Embodiment 4
With octadecylsilane chemically bonded silica is filling agent, and so that 0.005mol/L ammonium phosphate solution (is 4.8 with the phosphoric acid adjust pH)-methyl alcohol (60: 40) is moving phase, flow velocity 1ml/min detects wavelength 280nm.Sample thief, the accurate title, decide (to be equivalent to paracetamol 500mg approximately, Pamabrom 25mg in right amount, maleic acid neo-antergan 15mg), puts in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, the record chromatogram is measured peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 100.1%, RSD=0.44%, and the Pamabrom recovery is 100.4%, RSD=0.63%, the maleic acid neo-antergan recovery is 100.1%, RSD=0.55%.
This three component of evidence is used said method can obtain good separation detection effect.
With octadecylsilane chemically bonded silica is filling agent, and so that 0.005mol/L ammonium phosphate solution (is 4.7 with the phosphoric acid adjust pH)-acetonitrile (80: 20) is a moving phase, flow velocity 1ml/min detects wavelength 280nm.Sample thief, the accurate title, decide (to be equivalent to paracetamol 500mg approximately, Pamabrom 25mg in right amount, maleic acid neo-antergan 1 5mg), puts in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, the record chromatogram is measured peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 99.8%, RSD=0.37%, and the Pamabrom recovery is 100.1%, RSD=0.50%, the maleic acid neo-antergan recovery is 100.0%, RSD=0.56%.
This three component of evidence is used said method can obtain good separation detection effect.
Embodiment 6
With octadecylsilane chemically bonded silica is filling agent, and so that 0.005mol/L ammonium phosphate solution (is 5.0 with the phosphoric acid adjust pH)-methyl alcohol (60: 40) is moving phase, flow velocity 1ml/min detects wavelength 280nm.Sample thief, the accurate title, decide an amount of (being equivalent to paracetamol 500mg approximately, Pamabrom 25mg, maleic acid neo-antergan 15mg), put in the 100ml measuring bottle, add the moving phase dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 1ml, puts in the 10ml measuring bottle, add moving phase and be diluted to scale, shake up, precision is measured 20ul and is injected liquid chromatograph, record chromatogram (Fig. 3,1# paracetamol, 2# Pamabrom, the 3# neo-antergan, the 4# maleic acid), measure peak area; Other gets paracetamol, Pamabrom and maleic acid neo-antergan reference substance, and same mensuration calculated promptly respectively with peak area by external standard method.This law paracetamol recovery is 99.9%, RSD=0.41%, and the Pamabrom recovery is 100.3%, RSD=0.47%, the maleic acid neo-antergan recovery is 100.1%, RSD=0.52%.
This three component of evidence is used said method can obtain good separation detection effect.
Claims (4)
- A kind of detection method of pharmaceutical composition1, a kind of detection contains paracetamol, Pamabrom and maleic acid neo-antergan method for compositions, it is characterized in that: adopting high performance liquid chromatography, be 4.0～5.5 water with the pH value with the mixed solvent that is organic phase with alcohols or nitrile is to carry out separation determination in the system of moving phase.
- 2, according to claim 1, it is characterized in that: aqueous pH values is 4.3～5.2.
- 3, according to claim 2, it is characterized in that: aqueous pH values is 4.5～5.0.
- 4, according to claim 1, it is characterized in that organic phase is lower alcohols or nitrile, or the mixing of lower alcohols and nitrile.
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| CNB031544851A CN100348974C (en) | 2003-09-30 | 2003-09-30 | Pharmaceutical composition detection method |
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| CNB031544851A CN100348974C (en) | 2003-09-30 | 2003-09-30 | Pharmaceutical composition detection method |
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| CN1603815A CN1603815A (en) | 2005-04-06 |
| CN100348974C true CN100348974C (en) | 2007-11-14 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0081823A1 (en) * | 1981-12-10 | 1983-06-22 | WHITBY RESEARCH, Inc. | Composition for reducing menstrual pain |
| US4888343A (en) * | 1986-09-15 | 1989-12-19 | Bristol-Myers Company | Pharmaceutical compositions for relief of dysmenorrhea and/or premenstrual syndrome and process |
| US5306507A (en) * | 1992-03-26 | 1994-04-26 | Mallinckrodt Specialty Chemicals Company | Process and composition containing pamabrom and pyrilamine maleate |
| CN1426298A (en) * | 2000-04-19 | 2003-06-25 | 史密丝克莱恩比彻姆有限公司 | Composition |
-
2003
- 2003-09-30 CN CNB031544851A patent/CN100348974C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0081823A1 (en) * | 1981-12-10 | 1983-06-22 | WHITBY RESEARCH, Inc. | Composition for reducing menstrual pain |
| US4888343A (en) * | 1986-09-15 | 1989-12-19 | Bristol-Myers Company | Pharmaceutical compositions for relief of dysmenorrhea and/or premenstrual syndrome and process |
| US5306507A (en) * | 1992-03-26 | 1994-04-26 | Mallinckrodt Specialty Chemicals Company | Process and composition containing pamabrom and pyrilamine maleate |
| CN1426298A (en) * | 2000-04-19 | 2003-06-25 | 史密丝克莱恩比彻姆有限公司 | Composition |
Non-Patent Citations (3)
| Title |
|---|
| HPLC法测定感冒灵胶囊中各组分的含量 赵雪娥等.华西药学杂志，第13卷第4期 1998 * |
| HPLC法测定金扑感冒片中对乙酰氨基酚和咖啡因的含量 顾利红等.广东药学，第9卷第4期 1999 * |
| HPLC测定泰诺儿童退热液中对乙酰氨基酚的含量 蒋硕民等.中国现代应用药学杂志，第18卷第3期 2001 * |
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