CN107290448A - A kind of method of residual solvent in detection memantine - Google Patents
A kind of method of residual solvent in detection memantine Download PDFInfo
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- CN107290448A CN107290448A CN201710403899.5A CN201710403899A CN107290448A CN 107290448 A CN107290448 A CN 107290448A CN 201710403899 A CN201710403899 A CN 201710403899A CN 107290448 A CN107290448 A CN 107290448A
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- residual solvent
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a kind of method for detecting residual solvent in memantine, comprise the following steps：1) titer of residual solvent to be detected is prepared；2) need testing solution is prepared；3) by blank control, the titer and need testing solution of residual solvent to be detected are detected using gas chromatography, analyze the concentration of residual solvent；The residual solvent is at least one of acetic acid, ethylene glycol.The method of the present invention is simple to operate, the high boiling organic solvents such as ethylene glycol, the acetic acid that may be remained in bulk drug memantine in can qualitatively or quantitatively detecting, the residual for high boiling organic solvent in control bulk drug memantine production technology provides good reference.
Description
Technical field
The present invention relates to field of chemical detection, more particularly to a kind of method for detecting residual solvent in memantine.
Background technology
Residual solvent in medicine refers to what is used in bulk drug, auxiliary material and preparation are produced, but in technique productions
Fail the organic volatile compound removed completely.In bulk drug synthesis technique, select appropriate solvent can improve yield or
Determine the property of medicine.Therefore organic solvent is essential and very crucial material in drug synthetic reaction.Work as medicine
, will be to human body or environmental danger, therefore to the control of residual solvent when contained residual solvent level is higher than safety value
Increasingly paid close attention to by people.
The N-methyl-D-aspartate (NMDA) that memantine gates for noncompetitive, moderate strength quick voltage
Receptor antagonist, by delaying the release of Excitatory Neurotransmitter salt, is mainly used in treatment Alzheimer's disease (old
Dementia).The medicine is needed using dichloromethane, ethylene glycol, ethanol, acetonitrile, ethyl acetate, ether in preparation technology and may be used also
It can use the organic solvents such as acetic acid, chloroform.Dichloromethane, ethylene glycol, acetonitrile, chloroform belong to Equations of The Second Kind solvent, and should limit makes
With；And ethanol, ethyl acetate, acetic acid, ether belong to the 3rd class solvent, used in GMP or the limitation of other quality requirements, therefore have must
Their limit is control effectively in quality standard.
The content of the invention
It is an object of the invention to disclose a kind of method for detecting residual solvent in memantine.
The technical solution used in the present invention is：
The method of residual solvent, comprises the following steps in a kind of detection memantine：
1) titer of residual solvent to be detected is prepared；
2) need testing solution is prepared；
3) by blank control, the titer and need testing solution of residual solvent to be detected are examined using gas chromatography
Survey, analyze the concentration of residual solvent；The residual solvent is at least one of acetic acid, ethylene glycol.
It is preferred that, the titer of residual solvent to be detected is methanol solution.
It is preferred that, need testing solution is the methanol solution of memantine.
It is preferred that, blank control is the methanol solution of chromatographically pure.
It is preferred that, the chromatographic column of gas chromatography is fixed to adopt the dimethyl polysiloxane of 14% cyanogen propyl group phenyl -86%
The capillary column of phase.
It is preferred that, it is necessary to use fid detector detection temperature in gas chromatography, wherein 260 DEG C of detector temperature, sample introduction
Mouth temperature is 260 DEG C.
It is preferred that, the carrier gas condition of gas chromatography is：Using nitrogen, flow rate of carrier gas is 1.0ml/min, and split ratio is
20:1。
It is preferred that, the heating schedule of gas chromatography is：60 DEG C of column temperature, 240 DEG C are risen to 20 DEG C/min, keep 9min.
The beneficial effects of the invention are as follows：The method of the present invention is simple to operate, bulk drug hydrochloric acid in can qualitatively or quantitatively detecting
The high boiling organic solvents such as ethylene glycol, the acetic acid that may be remained in Memantine, for control bulk drug memantine production technology
The residual of middle high boiling organic solvent provides good reference.
Brief description of the drawings
Fig. 1 is embodiment blank solution chromatogram.
Fig. 2 is the gas chromatogram of embodiment standard solution.
Fig. 3 is embodiment need testing solution gas chromatogram.
Fig. 4 dimethyl sulfoxide (DMSO)s as blank solution gas chromatogram.
Fig. 5 is comparative example Plays product solution chromatogram.
Embodiment
Embodiment 1
(1) analysis method：Gas chromatography
Chromatographic system：
Chromatographic column：The dimethyl polysiloxane of 14% cyanogen propyl group phenyl -86% (refers to chromatogram for the capillary column of stationary phase
Post：Rtx-1701,30m × 0.25mm × 0.25um), fid detector.
Chromatographic parameter：
Chromatographic isolation parameter：Carrier gas：Nitrogen；Flow rate of carrier gas：1.0mL/min；Split ratio：20:1；
Fid detector temperature：260℃；Injector temperature：260℃；
Column temperature：60 DEG C, 240 DEG C are risen to 20 DEG C/min, 9min is kept；
Input mode：Direct injected；Sample size：1μL.
(2) solution is prepared：
1st, standard solution：
Standard items storing solution：Divide and accurately weigh ethylene glycol 62mg, glacial acetic acid 500mg in 100mL volumetric flasks, it is dilute with methanol
Release to scale, shake up, obtain standard items storing solution；
Prepare standard solution：Standard items storing solution 10mL accurately is measured in 100mL volumetric flask, with methanol dilution extremely
Scale, shakes up, and obtains standard solution；
2nd, need testing solution：
The test sample 0.5g of homemade memantine hydrochloride raw material medicine is accurately weighed, puts in 5mL volumetric flask, is dissolved with methanol
And scale is diluted to, shake up, be used as need testing solution.
(3) determination step
Sample introduction methanol is blank solution, and its chromatogram is as shown in Figure 1；
Sample introduction standard solution, obtains chromatogram, records the peak area of each standard items respective peaks, its chromatogram such as Fig. 2 institutes
Show；
Sample introduction need testing solution, records chromatogram, as shown in Figure 3；
It is each residual in peak area and need testing solution chromatogram by each standard items respective peaks in standard solution chromatogram
The peak area of solvent respective peaks is stayed, is calculated using below equation and obtains residual solvent ethylene glycol, second in bulk drug memantine
The content of acid：
Dissolvent residual (%)=A samples × V samples × C mark/(A marks × m samples) × 100%
In formula：A samples -- the peak area of residual solvent ethylene glycol, acetic acid in need testing solution；
The dilution volume of V samples -- test sample, Unit/mL；
C is marked -- the concentration of corresponding residual solvent, unit mg/mL in standard solution；
A is marked -- corresponding residual solvent peak peak area in standard solution；
The sample weighting amount of m samples -- test sample, unit mg；
Each detection data are substituted into above-mentioned formula, specific result of calculation is as follows：
Ethylene glycol (%) residual concentration is 0.054%.
Acetic acid (%) residual concentration is 0.41%.
Comparative example：
(1) analysis method：Gas chromatography
Chromatographic system：
Chromatographic column：By stationary phase of the methyl polysiloxane of 5% phenyl -95% capillary column (30m × 0.53mm ×
1.5um), fid detector.
Chromatographic parameter：
Chromatographic isolation parameter：Carrier gas：Nitrogen；Flow rate of carrier gas：1.0mL/min；Split ratio：10:1；
Fid detector temperature：280℃；Injector temperature：230℃；
Column temperature：50 DEG C, keep 12min；230 DEG C are risen to 30 DEG C/min, 12min is at least kept；
Input mode：Direct injected；Sample size：1μL.
(2) solution is prepared：
1st, standard solution：
Standard items storing solution：Divide and accurately weigh ethylene glycol 62mg, glacial acetic acid 500mg in 100mL volumetric flasks, use dimethyl
Sulfoxide is diluted to scale, shakes up, and obtains standard items storing solution；
Prepare standard solution：Standard items storing solution 10mL accurately is measured in 100mL volumetric flask, uses dimethyl sulfoxide (DMSO)
Scale is diluted to, is shaken up, standard solution is obtained.
(3) determination step
Sample introduction dimethyl sulfoxide (DMSO) is blank solution, and its chromatogram is as shown in Figure 4；
Sample introduction standard solution, obtains chromatogram, records the peak area of each standard items respective peaks, its chromatogram such as Fig. 5 institutes
Show；
By each in the peak area and blank solution chromatogram of each standard items respective peaks in standard of comparison product solution chromatogram
Knowable to the peak area of residual solvent respective peaks, the non-appearance of ethylene glycol, acetic acid.
This method can not detect ethylene glycol, acetic acid.
Claims (9)
1. a kind of method for detecting residual solvent in memantine, comprises the following steps：
1) titer of residual solvent to be detected is prepared；
2) need testing solution is prepared；
3) by blank control, the titer and need testing solution of residual solvent to be detected are detected using gas chromatography, point
Analyse the concentration of residual solvent；The residual solvent is at least one of acetic acid, ethylene glycol.
2. detection method according to claim 1, it is characterised in that the titer of the residual solvent to be detected is methanol
Solution.
3. detection method according to claim 1, it is characterised in that the need testing solution is the methanol of memantine
Solution.
4. detection method according to claim 1, it is characterised in that the blank control is the methanol solution of chromatographically pure.
5. detection method according to claim 1, it is characterised in that the chromatographic column of the gas chromatography is to adopt 14% cyanogen
The dimethyl polysiloxane of propyl group phenyl -86% is the capillary column of stationary phase.
6. detection method according to claim 1, it is characterised in that, it is necessary to use fid detector in the gas chromatography
Detection temperature, wherein 260 DEG C of detector temperature, injector temperature are 260 DEG C.
7. detection method according to claim 1, it is characterised in that the carrier gas condition of the gas chromatography is：Using
Nitrogen, flow rate of carrier gas is 1.0ml/min, and split ratio is 20:1.
8. detection method according to claim 1, it is characterised in that the heating schedule of the gas chromatography is：Column temperature
60 DEG C, 240 DEG C are risen to 20 DEG C/min, 9min is kept.
9. application of the claim 1~8 any one methods described in the U.S. bulk drug of hydrochloric acid Buddha's warrior attendant is prepared.
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| CN201710403899.5A CN107290448A (en) | 2017-06-01 | 2017-06-01 | A kind of method of residual solvent in detection memantine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109541112A (en) * | 2019-01-16 | 2019-03-29 | 苏州众合生物医药科技有限公司 | A kind of remaining method of ethyl alcohol in detection recombination human source anti-tnf-alpha project cleaning validation sample |
| CN112162045A (en) * | 2020-09-24 | 2021-01-01 | 石药集团欧意药业有限公司 | Method for detecting 2-chloropropane in memantine hydrochloride |
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| CN101038280A (en) * | 2007-04-11 | 2007-09-19 | 山东省医药工业研究所 | HPLC-ELSD measuring method for correlated matter in memantine hydrochloride |
| CN103713062A (en) * | 2013-12-31 | 2014-04-09 | 深圳出入境检验检疫局工业品检测技术中心 | Method for fast detection of residual amount of restricted organic solvents in textile |
| CN104297365A (en) * | 2014-09-17 | 2015-01-21 | 成都克莱蒙医药科技有限公司 | Determination method for residual solvent acetic acid in moxifloxacin hydrochloride |
| CN104458952A (en) * | 2014-12-08 | 2015-03-25 | 敖云霞 | Method for measuring solvent residue amounts of ethyl acetate and n-butyl alcohol in total flavonoids of herba epimedii |
| CN105203658A (en) * | 2015-09-16 | 2015-12-30 | 乐普药业股份有限公司 | Detection method for residual solvent in ezetimibe |
| CN105866267A (en) * | 2016-03-29 | 2016-08-17 | 福建中烟工业有限责任公司 | Method for extracting residual solvent in packaging material, method for detecting residual solvent, kit for detecting residual solvent, and use of kit |
-
2017
- 2017-06-01 CN CN201710403899.5A patent/CN107290448A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101038280A (en) * | 2007-04-11 | 2007-09-19 | 山东省医药工业研究所 | HPLC-ELSD measuring method for correlated matter in memantine hydrochloride |
| CN103713062A (en) * | 2013-12-31 | 2014-04-09 | 深圳出入境检验检疫局工业品检测技术中心 | Method for fast detection of residual amount of restricted organic solvents in textile |
| CN104297365A (en) * | 2014-09-17 | 2015-01-21 | 成都克莱蒙医药科技有限公司 | Determination method for residual solvent acetic acid in moxifloxacin hydrochloride |
| CN104458952A (en) * | 2014-12-08 | 2015-03-25 | 敖云霞 | Method for measuring solvent residue amounts of ethyl acetate and n-butyl alcohol in total flavonoids of herba epimedii |
| CN105203658A (en) * | 2015-09-16 | 2015-12-30 | 乐普药业股份有限公司 | Detection method for residual solvent in ezetimibe |
| CN105866267A (en) * | 2016-03-29 | 2016-08-17 | 福建中烟工业有限责任公司 | Method for extracting residual solvent in packaging material, method for detecting residual solvent, kit for detecting residual solvent, and use of kit |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109541112A (en) * | 2019-01-16 | 2019-03-29 | 苏州众合生物医药科技有限公司 | A kind of remaining method of ethyl alcohol in detection recombination human source anti-tnf-alpha project cleaning validation sample |
| CN112162045A (en) * | 2020-09-24 | 2021-01-01 | 石药集团欧意药业有限公司 | Method for detecting 2-chloropropane in memantine hydrochloride |
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