CN1996012A - Quality control method for ginsenoside-Rd medicament and preparation thereof - Google Patents
Quality control method for ginsenoside-Rd medicament and preparation thereof Download PDFInfo
- Publication number
- CN1996012A CN1996012A CN 200610051231 CN200610051231A CN1996012A CN 1996012 A CN1996012 A CN 1996012A CN 200610051231 CN200610051231 CN 200610051231 CN 200610051231 A CN200610051231 A CN 200610051231A CN 1996012 A CN1996012 A CN 1996012A
- Authority
- CN
- China
- Prior art keywords
- ginsenoside
- preparation
- quality control
- medicament
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Steroid Compounds (AREA)
Abstract
The gen-seng saponin-Rd medicine and dosage quality control mainly comprises characteristics, identification, check, finger print pattern, content testing and so on, through inspection of appearance characteristics identification, color spectrum identification and acid-base scale, protein, heavy metal, and so on to better control gen-seng sapoinin-Rd medicine and its agent quality, to ensure the safety of the medicine with better direction for production, and the production process being more rigid and reasonable.
Description
Technical field
The present invention is the method for quality control of a kind of ginsenoside-Rd medicament and preparation thereof, has comprised the quality control of ginsenoside-Rd raw material and preparation thereof, belongs to the technical field of drug quality control.
Background technology
Genseng, pseudo-ginseng contain multiple components, comprise volatile oil, fatty acid, carbohydrate, protein, alkaloid, steroidal, flavones and saponin etc.The researchist through experimental study, finds that the saponin of genseng, pseudo-ginseng is their effective constituent under the theoretical direction of the traditional Chinese medical science " promoting blood circulation and removing blood stasis ", total saponin can not reduce under cardiac output and the SI situation, and cardiac muscle power consumption and oxygen consumption are reduced; The arrhythmia cordis of antagonism several animal models; Resist myocardial ischemia/reperfusion injury; Effect such as platelet aggregation-against and hemangiectasis.Total saponin has the pharmacological action that drug for invigorating blood circulation and eliminating stasis has.Notoginseng total saponin has been made into parenteral solution (commodity thromboembolism by name is logical, XUESHUANTONG etc.) or tablet is used for treating the disease relevant with stagnation of QI-blood, as thrombosis of central vein of retina, cerebral ischemia, cerebral apoplexy, apoplexy sequela and antimigraine etc.Ginsenoside-rd is the monomer that separation and Extraction is come out from genseng, notoginseng total saponin, and action target spot is identical with notoginseng total saponin, can block specifically to be subjected to actuated Ca2+ passage.Ginsenoside-rd has the such characteristic promoting blood circulation and removing blood stasis of notoginseng total saponin equally, and the apoplexy card that comprises cranial vascular diseases such as cerebral hemorrhage cerebral infarction that syndrome of blood stasis is relevant has better therapeutic effect.Yet, in prior art, 2005 editions gensengs of Chinese Pharmacopoeia, the content assaying method that records under the pseudo-ginseng item has only provided the mensuration general ginsenoside, the method of quality control of arasaponin, from general ginsenoside, separation and purification is used for the treatment of facial paralysis due to the obstruction of collaterals by blood stasis in the arasaponin, speech is unfavorable, hemiplegia, the tongue nature stasis of blood is dim, diseases such as uneven pulse, also can be used for treating acute cerebrovascular diseases and cause the brain tissue ischemia/reperfusion injury, downright bad, see the monomer ginsenoside Rd of above patient and the preparation that uses this material to be prepared from, the method that does not also have quality control, thereby make that the quality control of ginsenoside Rd's medicine and preparation thereof is particularly important, the method of quality control that science must be arranged, just can guarantee the ordinary production of ginsenoside Rd's medicine and preparation thereof, guarantee the security of medication, can better instruct production, make controlling of production process strict more, rationally.The inventor has carried out the research of this method, and the method for quality control of ginsenoside-Rd medicament and preparation thereof is provided.
Summary of the invention
The objective of the invention is to: the method for quality control of a kind of ginsenoside Rd's medicine and preparation thereof is provided, and this method provides means, technical method of the index that detects, detection or the like to relevant production, testing agency; So that better control the quality of this medicine and preparation thereof, guarantee the security of medication, can better instruct production, make controlling of production process rationally strict more, make consumer's energy full appreciation product quality.
The present invention constitutes like this: the method for quality control of genseng soap former times-Rd medicine and preparation thereof, mainly comprise projects such as proterties, discriminating, inspection, finger-print, assay, it is with the detection index of ginsenoside-Rd reference substance as the quality control of ginsenoside-Rd medicament and preparation thereof.Specifically, the present invention is with discriminating, finger-print, the assay detection index of ginsenoside-Rd as ginsenoside-Rd medicament and preparation thereof.
The appearance character of ginsenoside-Rd medicament of the present invention and preparation thereof: under the situation that does not add pigment, ginsenoside-Rd medicament is white or micro-yellow powder; The liquid preparation of making is colourless to yellowish clear liquid; The solid pharmaceutical preparation of making is white or faint yellow to pale brown look.
The discrimination method of ginsenoside-Rd medicament of the present invention and preparation thereof: adopt thin-layered chromatography, sample pre-treatments comprises direct sample, makes need testing solution with the concentrated method of dissolving again of solvent dissolving or extraction back, and need testing solution generally uses silica G or silica G F
254Or silica gel H is a thin layer plate, the point sample amount is the arbitrary volume between 0.1～30 μ l, with ginsenoside-Rd product in contrast, developping agent can be formulated according to a certain percentage in chloroform, acetone, formic acid, water, methyl alcohol, methylene chloride, ethyl acetate, glacial acetic acid, the normal butyl alcohol one or more, and inspection method can be directly to inspect under visible light, under the ultraviolet light or spray method with chromogenic reagent.
The inspection of ginsenoside-Rd medicament of the present invention and preparation thereof: the whole projects such as inspection that comprise potential of hydrogen, protein, tannin, heavy metal, arsenic salt, oxalates, resin, potassium ion, microorganism, pyrogen, concrete detection method is identical with the method that current edition Chinese Pharmacopoeia appendix records, the detection method of potassium ion, heavy metal, arsenic salt also comprises with Microwave Digestion handles sample, and then adopts atomic absorption spectrophotometry, flame photometry, electrode method, titrimetry, plasma emission spectrum or inductive coupling plasma mass spectroscopy to carry out method for measuring; Technical requirement in the medicine is: (1) pH value is between 5.5～8.5, and (2) heavy metal is no more than 10/1000000ths, and (3) arsenic salt is no more than 2/1000000ths.
The inspection of the related substance of ginsenoside-Rd medicament of the present invention and preparation thereof: sample pre-treatments comprises direct sample, concentrates the method for dissolving again with the solvent dissolving or after extracting, make need testing solution, get 1～10% need testing solution and make solution with the test sample equal volume, product generally use silica G or silica G F in contrast
254Or silica gel H is a thin layer plate, the point sample amount is the arbitrary volume between 0.1～30 μ l, developping agent can be formulated according to a certain percentage in chloroform, acetone, formic acid, water, methyl alcohol, methylene chloride, ethyl acetate, glacial acetic acid, the normal butyl alcohol one or more, inspection method can be directly to inspect under visible light, under the ultraviolet light or spray method with chromogenic reagent, the spot that spot that need testing solution produces and reference substance solution produce compares, and color must not be darker.
High performance liquid chromatography is adopted in the finger-print inspection of ginsenoside-Rd medicament of the present invention and preparation thereof, and sample pre-treatments comprises direct sample, concentrates the method for dissolving again with the solvent dissolving or after extracting, and makes need testing solution, uses C
8～C
18The chromatographic column of type filler, is moving phase with one or more kind solvents in second eyeball, water, methyl alcohol, the phosphoric acid under the proper ratio condition of routine, detect wavelength in 200～354nm scope, inject high performance liquid chromatograph, the record chromatographic peak, with the ginsenoside-Rd reference substance as the characteristic fingerprint peak, and the deduction solvent peak, must not cross 10.0% with other impurity peaks that the peak area value normalization method records except that main peak.
The content assaying method of ginsenoside-Rd medicament of the present invention and preparation thereof: adopt high performance liquid chromatography, sample pre-treatments comprises direct sample, concentrate the method for dissolving again with the solvent dissolving or after extracting, make need testing solution, use the chromatographic column of C8～C18 type filler, with the second eyeball, water, methyl alcohol, one or more kind solvents in the phosphoric acid are moving phase under the proper ratio condition of routine, with ginsenoside-Rd product in contrast, detect wavelength in 200～354nm scope, inject high performance liquid chromatograph, the record chromatographic peak, measure, calculate, promptly.Concrete method is: sample pre-treatments comprises direct sample, extracts the concentrated method of dissolving again in back with the solvent dissolving, make need testing solution, using the chromatographic column of C18 type filler, is moving phase with methyl alcohol, water under conventional proper ratio condition, with ginsenoside-Rd product in contrast, detect wavelength at 203nm, inject high performance liquid chromatograph, the record chromatographic peak is measured, calculate, promptly.
Being used for described in the present invention dissolves or the solvent that extracts ginsenoside-Rd medicament includes but not limited to: the potpourri of one or more of water, acetonitrile, methyl alcohol, ethanol, propylene glycol, methylene chloride, methenyl choloride, ethyl acetate, normal butyl alcohol, toluene, benzene, acetone.
Compared with prior art, method of quality control provided by the invention can better be controlled the product quality of ginsenoside Rd's medicine and preparation thereof, guarantee the security of medication, after using the present invention, can guarantee the quality of finished drug product, from production, raw material quality control, all must carry out to the processing step of each production run, otherwise product just might not satisfy quality requirements in strict accordance with technological procedure; We find when testing: adopt the present invention will require ginsenoside Rd's content to reach more than 90%, otherwise underproof situation can appear in manufactured goods; So more help instruct producing, make technology controlling and process rationally strict more, allow consumer's full appreciation product quality, this similar drug of relieved use.The detection index that the present invention chooses is the effective active composition of product, is very necessary to the control drug quality, and is very desirable as the index of content control.Sensitivity was low when the applicant found the ginsenoside Rd under study for action owing to the terminal absorption of ultraviolet detection, noise effect is big, and Interference Peaks is arranged, be difficult to use, therefore, the inventor is that moving phase is tested through methanol-water, acetonitrile-aqueous solution in varing proportions, is under the moving phase condition at methanol-water under conventional proper ratio condition finally; Simultaneously, according to the panaxoside Pd ultra-violet absorption spectrum, select 203nm for detecting wavelength, panaxoside Pd and other compositions can reach baseline separation under this condition, number of theoretical plate calculates by the panaxoside Pd peak can reach 1500～3000, can reach more than 5 with separate impurities degree in the sample, and the result shows, chromatographic peak type at 203nm ginsenoside Rd medicine is better, and the finger-print that obtains can be good at the testing product quality.So the present invention has selected the technological means of a series of method as control, testing product quality, make the production technology of implementing ginsenoside Rd's medicine and preparation thereof that guarantee arranged, the preparation that obtains is more reliable, has reached the purpose of invention.
Utilize method of quality control provided by the invention for proof and can better control the product quality of ginsenoside Rd's medicine and preparation thereof, the medicine that obtains has effective effect, and the applicant has carried out a series of experiments;
The research of experimental example 1 efficient liquid-phase chromatograph finger print atlas
1, the selection of moving phase
Investigated (1) methanol-water, (2) second eyeball-water in the research process respectively, the result shows that moving phase is better with methanol-water (75: 25) peak shape, goes out the peak fully and be evenly distributed, so finally selected.
2, detect wavelength determination
According to the panaxoside Pd ultra-violet absorption spectrum, the 203nm place is ginsenoside Rd's maximum absorption band in the research, finally selects for use 203nm as detecting wavelength.
3, ginsenoside Rd's reference substance, raw material and injection high-efficient liquid phase chromatogram spectrum (seeing accompanying drawing 1,2)
The result shows, retention time between ginsenoside Rd's reference substance, raw material and finished product injection three, peak shape are identical, and good correlativity is arranged, and ginsenoside Rd's finger-print of the applicant's research can the better controlled product quality.
Experimental example 2 content assaying methods are learned research
(1) instrument and reagent
High performance liquid chromatograph: Tianjin, island LC-6A infusion pump, CR-3A data processor, SPD-6A UV, visible light detecting device.
Methyl alcohol: chromatographically pure, water: redistilled water
Panaxoside Pd reference substance: self-control; Purity testing:
1.TLCS method: λ
S=530nm, λ
R=700nm, point sample 100 μ g do not detect impurity peaks.
2.HPLC method: condition determination is according to the method for assay, sample introduction 40 μ g, and the peak area normalization method records purity=99.67%, RSD=0.18%; Sample introduction 100 μ g record purity=98.92%, RSD=0.11%.
(2) chromatographic condition and system suitability test chromatographic column: Nucleosil-ODS, 5um, 4.6mm * 150mm, (or 4.6mm * 250mm); Moving phase: methanol-water (75: 25); Detect wavelength:, select 203nm for detecting wavelength according to the panaxoside Pd ultra-violet absorption spectrum; Column temperature: room temperature; Flow: 0.8ml/min; Panaxoside Pd and other compositions can reach baseline separation under this condition, number of theoretical plate calculates by the panaxoside Pd peak can reach 1500～3000, can reach more than 5 with separate impurities degree in the sample, so the body specified number of theoretical plate should be not less than 1500, degree of separation is not less than 1.5.
(3) investigation of linear relationship: accurate panaxoside Pd reference substance solution (C=0.025mg/ml) 0.5,1,2,5,7.5, the 10ul sample introduction drawn, measure the peak area integrated value by above-mentioned chromatographic condition, the results are shown in Table 1:
Table 1:
| Numbering | Sample size W (μ g) | |
| 1 2 3 4 5 6 | 1.012 2.025 4.050 10.12 15.19 20.25 | 249108.1 572803.9 1055380.0 2854280.0 4226880.0 5652161.0 |
With sample size W (μ g) is horizontal ordinate, and peak area A is an ordinate, gets regression equation: A=-29072.2+280833.6W, r=0.99988, linear extent: 1.01～20.25 μ g.
(4) the accurate absorption of precision test reference substance solution is an amount of, and continuous sample introduction 5 times records panaxoside Pd peak area score value, calculates relative standard deviation RSD＜1.5%, the results are shown in Table 2.
Table 2:
| NO. | |
| 1 144,495 2 144,046 3 143,100 4 143,465 5 147327 mean value RSD (%) | 144486.6 1.16 |
(5) the same reference substance solution of stability test is measured by above-mentioned condition interval sample introduction, and peak area score value RSD=2.10% the results are shown in Table 3.
Table 3:
| Time (hour) | Peak area |
| 12468 12 24 28 mean value RSD (%) | 144085 148194 140315 143205 145036 139990 141666 147084 143697 2.1 |
(6) replica test: precision takes by weighing this product 10mg, and totally 5 parts, in the 10ml measuring bottle, make need testing solution with dissolve with methanol, precision takes by weighing reference substance 10mg simultaneously, makes reference substance solution with method, respectively gets the 10ul sample introduction, measures result of calculation such as table 4:
Table 4:
| NO. | Content (%) |
| 12345 mean value RSD (%) | 93.06 91.02 89.38 90.13 90.98 90.91 1.52 |
(7) recovery test: adopt the application of sample absorption method.Get 6 parts in the sample that records content, it is an amount of to add the panaxoside Pd reference substance solution respectively, presses the described method of text, conditional operation, with the following formula calculate recovery rate, the results are shown in Table 5:
Table 5
| Numbering | Amount in the sample (μ g) | Add reference substance amount (μ g) | Record total amount (μ g) | Recovery n=3 (%) |
| 123456 mean value RSD (%) | 0.9539 0.9539 0.9539 0.9539 0.9539 0.9539 | 0.30375 0.30375 0.4253 0.4253 1.0125 1.0125 | 1.2490 1.2530 1.3912 1.3800 1.9764 1.9495 | 97.15 98.47 102.82 100.20 100.99 98.33 99.66 2.08 |
(8) sample determination: get three batches of this product, press the described method of text, conditional operation respectively, standard law is calculated content, table 6 as a result in addition:
Table 6:
| Lot number | The result |
| 980303 980812 981215 | 90.91％ 93.17％ 96.49％ |
Concrete embodiment:
Embodiments of the invention 1: the method for quality control of ginsenoside-Rd medicament mainly comprises projects such as proterties, discriminating, inspection, finger-print, assay.
1, proterties: this product is white or micro-yellow powder; Odorless.
2, differentiate: it is an amount of to get this product, adds the solution that methyl alcohol is made every 1mg/1ml, as need testing solution.It is an amount of that other gets the panaxoside Pd reference substance, adds methyl alcohol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin-layered chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel H thin layer plate of bonding agent with the sodium carboxymethyl cellulose, the upper strata liquid of placing layering with normal butyl alcohol-ethyl acetate-water (4: 1: 5) below 15 ℃ is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on show the spot of same color.
3, check the inspection of (1) ginsenoside-Rd medicament: the whole projects such as inspection that comprise potential of hydrogen, loss on drying, residue on ignition, protein, tannin, heavy metal, arsenic salt, oxalates, resin, potassium ion, pyrogen, concrete detection method is identical according to the method that 2005 editions pharmacopeia appendix record, technical requirement in the medicine is: (1) moisture content must not cross 4.0, (2) heavy metal is no more than 10/1000000ths, and (3) arsenic salt is no more than 2/1000000ths.
(2) it is an amount of that 1. related substance takes by weighing this product, adds dissolve with methanol and make the solution that every 1ml contains 10mg, as need testing solution; The accurate 0.1ml that draws adds methyl alcohol and is diluted to 2ml, in contrast solution.Test according to thin-layered chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of bonding agent with the sodium carboxymethyl cellulose, (4: 2: 1: 2) subnatant of the layering of placement below 15 ℃ was a developping agent with normal butyl alcohol-chloroform-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, major impurity spot and contrast solution relatively must not be darker.
2. by [assay] operation down, draw the need testing solution 5ul under the related substance inspection 1., inject liquid chromatograph, the record chromatographic peak, with the ginsenoside-Rd reference substance as the characteristic fingerprint peak, the deduction solvent peak, other impurity peaks that records except that main peak with the peak area value normalization method is no more than 10.0%.
4, assay is according to high performance liquid chromatography (attached VID of Chinese Pharmacopoeia version in 2005) test.
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filling agent, and methanol-water (75: 25) is a moving phase, and the detection wavelength is 203nm; Theoretical cam curve is calculated with the panaxoside Pd peak should be not less than 1500, and the degree of separation of panaxoside Pd chromatographic peak and impurity peaks should be up to specification.
The preparation of need testing solution: it is an amount of that precision takes by weighing this product, with dissolve with methanol, makes the solution that every 1ml contains 1mg, shakes up, and filters with the 0.45um miillpore filter, and filtrate is as need testing solution.
The preparation of reference substance solution: precision takes by weighing through dry 48 hours panaxoside Pd reference substance of phosphorus pentoxide an amount of, adds dissolve with methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.
Determination method: above-mentioned two kinds of each 10ul of solution of accurate respectively absorption, inject liquid chromatograph, measure, calculate, promptly.
Embodiments of the invention 2: the method for quality control of ginsenoside-Rd injection mainly comprises projects such as proterties, discriminating, inspection, finger-print, assay.
1, proterties this product is colourless or yellowish supernatant liquid.
2, this product 1ml is got in discriminating, water bath method, and residue is with methyl alcohol 10ml dissolving, and supernatant is as need testing solution.It is an amount of that other gets the panaxoside Pd reference substance, adds methyl alcohol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin-layered chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution 5ul, put respectively in same be on the silica gel H thin layer plate of bonding agent with the sodium carboxymethyl cellulose, the upper strata liquid of placing layering with normal butyl alcohol-ethyl acetate-water (4: 1: 5) below 15 ℃ is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on show the spot of same color.
3, check the inspection of (1) ginsenoside-Rd injection: the inspection etc. that comprises potential of hydrogen, protein, tannin, heavy metal, arsenic salt, oxalates, resin, potassium ion, aseptic, pyrogen is projects all, concrete detection method is identical according to the method that 2005 editions pharmacopeia appendix record, the detection method of potassium ion, heavy metal, arsenic salt also comprises with Microwave Digestion handles sample, and then adopts atomic absorption spectrophotometry, flame photometry, electrode method, titrimetry, plasma emission spectrum or inductive coupling plasma mass spectroscopy to carry out method for measuring; Technical requirement in the medicine is: (1) pH value is between 5.5～8.5, and (2) heavy metal is no more than 10/1000000ths, and (3) arsenic salt is no more than 2/1000000ths.
(2) related substance 1. precision measure this product 1ml, water bath method, the accurate methyl alcohol 1ml that adds of residue makes dissolving, centrifugal, supernatant is as need testing solution; Accurate this solution 0.1ml that draws adds methyl alcohol and is diluted to 2ml, in contrast solution.Test according to thin-layered chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of bonding agent with the sodium carboxymethyl cellulose, (4: 2: 1: 2) subnatant of the layering of placement below 15 ℃ was a developping agent with normal butyl alcohol-chloroform-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, major impurity spot and contrast solution relatively must not be darker.
2. by [assay] operation down, draw the need testing solution 5ul under the related substance inspection 1., inject liquid chromatograph, the record chromatographic peak, with the ginsenoside-Rd reference substance as the characteristic fingerprint peak, the deduction solvent peak must not cross 10.0% with other impurity peaks that the peak area value normalization method records except that main peak.
4, assay is according to high performance liquid chromatography (2005 editions appendix VID of Chinese Pharmacopoeia) test.
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filling agent, and methanol-water (75: 25) is a moving phase, and the detection wavelength is 203nm; Theoretical cam curve is calculated with the panaxoside Pd peak, should be not less than 1500, and the degree of separation of panaxoside Pd chromatographic peak and impurity peaks should be up to specification.
The preparation of need testing solution: accurate this product 1ml that draws, put in the 10ml measuring bottle, add methyl alcohol and be diluted to scale, shake up, filter with the 0.45um miillpore filter, filtrate is as the solution of test sample.
The preparation of reference substance solution: precision takes by weighing through dry 48 hours panaxoside Pd reference substance of phosphorus pentoxide an amount of, adds dissolve with methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.
Determination method: above-mentioned two kinds of each 10ul of solution of accurate respectively absorption, inject liquid chromatograph, measure, calculate, promptly.
Embodiments of the invention 3: the method for quality control of ginsenoside-Rd dripping pill mainly comprises projects such as proterties, discriminating, inspection, finger-print, assay.
1, proterties this product is white or faint yellow sphere or the spherical preparation of class to pale brown look.
2,1 of this product is got in discriminating, adds dissolve with methanol, filter, and the filtrate water bath method, residue is with methyl alcohol 10ml dissolving, and supernatant is as need testing solution.It is an amount of that other gets the panaxoside Pd reference substance, adds methyl alcohol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin-layered chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution 5ul, put respectively in same be on the silica gel H thin layer plate of bonding agent with the sodium carboxymethyl cellulose, the upper strata liquid of placing layering with normal butyl alcohol-ethyl acetate-water (4: 1: 5) below 15 ℃ is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on show the spot of same color.
3, check the inspection of (1) ginsenoside-Rd dripping pill: comprise whole projects such as inspection of weight differential, dissolve scattered time limit, microbial limit, concrete detection method is identical according to the method that 2005 editions pharmacopeia appendix record; Technical requirement in the medicine is: (1) weight differential is ± 12%, and (2) dissolve scattered time limit is 〉=30 minutes.
(2) related substance 1. precision take by weighing this product 50mg, add dissolve with methanol, filter, the filtrate water bath method, the accurate methyl alcohol 1ml that adds of residue makes dissolving, centrifugal, supernatant is as need testing solution; Accurate this solution 0.1ml that draws adds methyl alcohol and is diluted to 2ml, in contrast solution.Test according to thin-layered chromatography (2005 editions appendix VIB of Chinese Pharmacopoeia), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of bonding agent with the sodium carboxymethyl cellulose, (4: 2: 1: 2) subnatant of the layering of placement below 15 ℃ was a developping agent with normal butyl alcohol-chloroform-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing in 110 ℃.In the test sample chromatogram, major impurity spot and contrast solution relatively must not be darker.
2. by [assay] operation down, draw the need testing solution 5ul under the related substance inspection 1., inject liquid chromatograph, the record chromatographic peak, with the ginsenoside-Rd reference substance as the characteristic fingerprint peak, the deduction solvent peak must not cross 10.0% with other impurity peaks that the peak area value normalization method records except that main peak.
4, assay is according to high performance liquid chromatography (2005 editions appendix VID of Chinese Pharmacopoeia) test.
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filling agent, and methanol-water (75: 25) is a moving phase, and the detection wavelength is 203nm; Theoretical cam curve is calculated with the panaxoside Pd peak, should be not less than 1500, and the degree of separation of panaxoside Pd chromatographic peak and impurity peaks should be up to specification.
The preparation of need testing solution: precision takes by weighing this product 50mg (1), puts in the 10ml measuring bottle, and it is an amount of to add methyl alcohol, and heating makes dissolving, is cooled to room temperature, is diluted to scale with methyl alcohol, shakes up, and filters with the 0.45um miillpore filter, gets the solution of subsequent filtrate as test sample.
The preparation of reference substance solution: precision takes by weighing through dry 48 hours panaxoside Pd reference substance of phosphorus pentoxide an amount of, adds dissolve with methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.
Determination method: above-mentioned two kinds of each 10ul of solution of accurate respectively absorption, inject liquid chromatograph, measure, calculate, promptly.
Description of drawings:
Fig. 1, Fig. 2 are raw material and preparation HPLC figure
Among Fig. 1,2: 1-blank 2-reference substance 3-raw material 4-preparation
Claims (10)
1, the method for quality control of a kind of ginsenoside-Rd medicament and preparation thereof, mainly comprise projects such as proterties, discriminating, inspection, finger-print, assay, it is characterized in that: it is with the detection index of ginsenoside-Rd reference substance as the quality control of ginsenoside-Rd medicament and preparation thereof.
2, the method for quality control of ginsenoside-Rd medicament according to claim 1 and preparation thereof is characterized in that: with the detection index of ginsenoside-Rd as the discrimination method of ginsenoside-Rd medicament and preparation thereof, finger-print, assay.
3, the method for quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof is characterized in that: proterties is: ginsenoside-Rd medicament is white or micro-yellow powder; Liquid preparation in the ginsenoside-Rd medicament preparation is colourless to yellowish clear liquid; Solid pharmaceutical preparation is a white or faint yellow to pale brown look.
4, the method for quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof, it is characterized in that: the ginsenoside-Rd discrimination method: adopt thin-layered chromatography, sample pre-treatments comprises direct sample, makes need testing solution with the concentrated method of dissolving again of solvent dissolving or extraction back, and need testing solution generally uses silica G or silica G F
254Or silica gel H is a thin layer plate, the point sample amount is the arbitrary volume between 0.1～30 μ l, with ginsenoside-Rd product in contrast, developping agent can be formulated according to a certain percentage in chloroform, acetone, formic acid, water, methyl alcohol, methylene chloride, ethyl acetate, glacial acetic acid, the normal butyl alcohol one or more, and inspection method can be directly to inspect under visible light, under the ultraviolet light or spray method with chromogenic reagent.
5, the method of quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof, it is characterized in that: the inspection of ginsenoside-Rd medicament and preparation thereof: comprise potential of hydrogen, protein, tannin, heavy metal, arsenic salt, oxalates, resin, potassium ion, pyrogen, the inspections of microorganism and various preparation inspection items etc. are project all, concrete detection method is identical with the method that current edition Chinese Pharmacopoeia appendix records, potassium ion, heavy metal, the detection method of arsenic salt also comprises with Microwave Digestion handles sample, and then adopts atomic absorption spectrophotometry, flame photometry, the electrode method, titrimetry, plasma emission spectrum or inductive coupling plasma mass spectroscopy are carried out method for measuring; Technical requirement in ginsenoside Rd's medicine and the injection thereof is: (1) pH value is between 5.5～8.5, and (2) heavy metal is no more than 10/1000000ths, and (3) arsenic salt is no more than 2/1000000ths.
6, the method for quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof, it is characterized in that: the inspection of medicine ginsenoside-Rd and preparation related substance thereof: sample pre-treatments comprises direct sample, concentrates the method for dissolving again with the solvent dissolving or after extracting, make need testing solution, get 1～10% need testing solution and make solution with the test sample equal volume, product generally use silica G or silica G F in contrast
254Or silica gel H is a thin layer plate, the point sample amount is the arbitrary volume between 0.1～30 μ l, developping agent can be formulated according to a certain percentage in chloroform, acetone, formic acid, water, methyl alcohol, methylene chloride, ethyl acetate, glacial acetic acid, the normal butyl alcohol one or more, inspection method can be directly to inspect under visible light, under the ultraviolet light or spray method with chromogenic reagent, the spot that spot that need testing solution produces and reference substance solution produce compares, and color must not be darker.
7, the method for quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof, it is characterized in that: the ginsenoside-Rd finger-print is checked, adopt high performance liquid chromatography, sample pre-treatments comprises direct sample, concentrates the method for dissolving again with the solvent dissolving or after extracting, make need testing solution, use C
8～C
18The chromatographic column of type filler, is moving phase with one or more kind solvents in second eyeball, water, methyl alcohol, the phosphoric acid under the proper ratio condition of routine, detect wavelength in 200～350nm scope, inject high performance liquid chromatograph, the record chromatographic peak, with the ginsenoside-Rd reference substance as the characteristic fingerprint peak, and the deduction solvent peak, must not cross 10.0% with other impurity peaks that the peak area value normalization method records except that main peak.
8, the method for quality control of ginsenoside-Rd medicament according to claim 1 and 2 and preparation thereof, it is characterized in that: the content assaying method of ginsenoside-Rd: adopt high performance liquid chromatography, sample pre-treatments comprises direct sample, concentrates the method for dissolving again with the solvent dissolving or after extracting, make need testing solution, use C
8～C
18The chromatographic column of type filler, is moving phase with one or more kind solvents in second eyeball, water, methyl alcohol, the phosphoric acid under the proper ratio condition of routine, with ginsenoside-Rd product in contrast, detect wavelength in 200～350nm scope, inject high performance liquid chromatograph, the record chromatographic peak is measured, calculate, promptly.
9, the method for quality control of ginsenoside-Rd medicament according to claim 8 and preparation thereof, it is characterized in that: the assay of ginsenoside-Rd: with high effective liquid chromatography for measuring, sample pre-treatments comprises direct sample, extracts the concentrated method of dissolving again in back with the solvent dissolving, make need testing solution, use C
18The chromatographic column of type filler is moving phase with methyl alcohol, water under conventional proper ratio condition, with ginsenoside-Rd product in contrast, detects wavelength at 203nm, injects high performance liquid chromatograph, and the record chromatographic peak is measured, and calculates, promptly.
10, according to the method for quality control of described ginsenoside-Rd medicament of claim 4～9 and preparation thereof, it is characterized in that: solvent includes but not limited to: the potpourri of one or more in water, acetonitrile, methyl alcohol, ethanol, propylene glycol, methylene chloride, methenyl choloride, ethyl acetate, normal butyl alcohol, toluene, benzene, the acetone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051231 CN1996012A (en) | 2006-09-26 | 2006-09-26 | Quality control method for ginsenoside-Rd medicament and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051231 CN1996012A (en) | 2006-09-26 | 2006-09-26 | Quality control method for ginsenoside-Rd medicament and preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1996012A true CN1996012A (en) | 2007-07-11 |
Family
ID=38251155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610051231 Pending CN1996012A (en) | 2006-09-26 | 2006-09-26 | Quality control method for ginsenoside-Rd medicament and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1996012A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058643A (en) * | 2009-11-17 | 2011-05-18 | 天津天士力制药股份有限公司 | Ginseng saponin H extract and preparation method thereof |
| CN102058644B (en) * | 2009-11-17 | 2013-09-11 | 天士力制药集团股份有限公司 | Ginseng saponin H extract and preparation method thereof |
-
2006
- 2006-09-26 CN CN 200610051231 patent/CN1996012A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058643A (en) * | 2009-11-17 | 2011-05-18 | 天津天士力制药股份有限公司 | Ginseng saponin H extract and preparation method thereof |
| CN102058643B (en) * | 2009-11-17 | 2013-09-11 | 天士力制药集团股份有限公司 | Ginseng saponin H extract and preparation method thereof |
| CN102058644B (en) * | 2009-11-17 | 2013-09-11 | 天士力制药集团股份有限公司 | Ginseng saponin H extract and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101653899B1 (en) | Method for extracting and separating ginkgolides | |
| CN100578219C (en) | Detection method for Chinese medicine injection made from radix salvia miltiorrhiza and safflower | |
| CN102028923B (en) | Quality control method of Wujiashenghua capsules | |
| CN104569170B (en) | A kind of detection method of ginkgo-dipyridamine injection | |
| CN101851261B (en) | Polygonum perfoliatum medicinal material, method for preparing reference substance of active constituents in preparation thereof as well as content determination method | |
| CN104013710B (en) | A kind of Cape jasmine cypress composition and its detection method | |
| CN102353733B (en) | Quality detection method for Ruyi Zhenbao preparation | |
| CN105891404A (en) | Quality control method for traditional Chinese medicine oral liquid for treating psoriasis | |
| CN102854281A (en) | Detection method of sugar-free strong loquat syrup | |
| CN102353732A (en) | Quality detection method of Zhenlong brain-refreshment preparation | |
| CN100387243C (en) | Quality control method of ixeris sonchifolia injection | |
| CN102068549B (en) | Detection method for Chinese medicinal preparation heat clearing and blood cooling pills | |
| CN102441057B (en) | High performance liquid chromatography (HPLC) fingerprint detection method for blood-nourishing brain-refreshing grain | |
| CN102274401A (en) | Traditional Chinese medicine preparation for treating gastropathy and preparation method and detection method thereof | |
| CN103169864B (en) | Zengye Tang granule and preparation method thereof, purposes and detection method | |
| CN101204434A (en) | Quality standard for thrombus dispelling pill and test method thereof | |
| CN108627581A (en) | Rhynchophyllin and isorhynchophylline content assaying method in a kind of Xiao ' erqixingcha particle | |
| CN1996012A (en) | Quality control method for ginsenoside-Rd medicament and preparation thereof | |
| CN100574792C (en) | A kind of effective ingredient detection method of Chinese medicine composition | |
| CN1853674B (en) | Quality controlling method of Xingdan injection | |
| CN100570358C (en) | Treat the detection method of asthenopic pharmaceutical preparation | |
| CN102707006A (en) | Quality detection method of cudrania tricuspidata formula granules | |
| CN101156894B (en) | Detection method of apricot red injection | |
| CN109470801A (en) | The method for building up and its standard finger-print of a kind of rhizoma dioscoreae nipponicae efficient liquid-phase chromatograph finger print atlas and application | |
| CN1951417A (en) | Quality control method of a pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |