CN107884500A - The method that LC-MS detects flunarizine in Chinese patent drug and health food - Google Patents
The method that LC-MS detects flunarizine in Chinese patent drug and health food Download PDFInfo
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- CN107884500A CN107884500A CN201711366205.1A CN201711366205A CN107884500A CN 107884500 A CN107884500 A CN 107884500A CN 201711366205 A CN201711366205 A CN 201711366205A CN 107884500 A CN107884500 A CN 107884500A
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- flunarizine
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- 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
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Abstract
The invention discloses the method for flunarizine in a kind of LC-MS detection Chinese patent drug and health food, comprise the following steps：(1) reference substance solution is prepared：Take flunarizine reference substance that reference substance solution is made with methanol；(2) testing sample solution is prepared：Take auxiliary improvement of memory class Chinese medicine preparation and health food using methanol extract, and will extract resulting solution it is purified testing sample solution；(3) reference substance solution and testing sample solution upper liquid matter combined instrument is taken to carry out qualitative, quantitative measure to the flunarizine in need testing solution.Method provided by the invention is detected by the way of multiple-reaction monitoring, interference less, high sensitivity, testing result it is accurate.
Description
Technical field
The present invention relates to the detection method of flunarizine, more particularly to a kind of LC-MS detection Chinese patent drug and health food
The method of middle flunarizine.
Background technology
Flunarizine has nootropic effect, but it is mainly used in Andre Meynier syndrome, vascular headache and cerebral arteriovenous malformation,
And it can be used for treating acute ischemic cerebrovascular disease, such as cerebral thrombus, cerebral embolism, transient cerebral ischemia；To hypertension
Caused orthostatic dizziness, tinnitus etc. are also effective.But it can produce poor appetite, Nausea and vomiting, dry, headache, palpitaition, dermatitis
Deng side effect.
In recent years, with the expansion being continuously increased with astogeny society of social competition's pressure, in auxiliary improvement of memory class
Patent medicine and health products have sizable market in consumer.It is non-in health products but some illegal retailers are possessed with a lust for gain
Method adds chemicals, is then illegally publicized, is sought exorbitant profit so as to delude the masses again.For many years, pharmaceuticals administration portion
Door never stops the focus efforts on special areas to illegally adding and strike, but is lured in face of huge market, and illegal businessman still quickly walks
Danger, western medicine composition is stealthily illegally added in Chinese patent drug and health food.At present, auxiliary improvement of memory class health food may be non-
Method adds medicine, including flunarizine, is illegally added currently used for auxiliary improvement of memory class Chinese medicine preparation and health food
Screening method it is less, it is therefore necessary to whether containing flunarizine in auxiliary improvement of memory class Chinese medicine preparation and health food
Detected, for preventing and supervising auxiliary improvement of memory class Chinese patent drug and health food into caused adverse events behind market
Occur, it is ensured that security, it is necessary to establish in auxiliary improvement of memory class Chinese medicine preparation and health food flunarizine it is fast
Fast screening method.
The content of the invention
The method that the purpose of the present invention aims to provide flunarizine in a kind of LC-MS detection Chinese patent drug and health food.
The purpose of the present invention is achieved through the following technical solutions：In a kind of LC-MS detection Chinese patent drug and health food
The method of flunarizine, comprises the following steps：
(1) reference substance solution is prepared：Take flunarizine reference substance that reference substance solution is made with methanol；
(2) testing sample solution is prepared：Auxiliary improvement of memory class Chinese medicine preparation and health food is taken to be extracted using methanol, and
To extract resulting solution it is purified testing sample solution；
(3) reference substance solution and testing sample solution upper liquid matter combined instrument is taken to carry out the flunarizine in need testing solution
Qualitative, quantitative determines, wherein,
Chromatographic condition：3.0mm × 100mm, 1.8 μm, Eclipse XDB C18Chromatographic column, flow velocity：0.30ml·min-1,
Column temperature：40 DEG C, sample size:1μl；ESI holotypes：Mobile phase A is 0.1% formic acid solution, and Mobile phase B is methanol；Gradient elution
Program：0~2min, 92%A, 10%B；2~10min, 92%~8%A, 8%~92%B；10~13min, 10%A, 92%
B；2min is balanced under 90%A, 10%B；ESI negative modes：Mobile phase A is water, and Mobile phase B is acetonitrile；Gradient elution program:0
~0.5min, 85%A, 15%B；0.5~3min, 85%~10%A, 15%~90%B；3~5min, 15%A, 85%B；
2min is balanced under 85%A, 15%B；
Mass Spectrometry Conditions：Electric spray ion source (ESI), negative ions pattern, multiple-reaction monitoring (MRM) scan mode：M/z is
405.2/200.1, fragmentation voltage 100V, impact energy 50V, retention time 8.5min, temperature degree is dried：360 DEG C, atomizer pressure
Power：40Psi, dry gas stream speed：10L·min–1。
In the step (1), the dissolving of flunarizine reference substance methanol is taken to be configured to the flunarizine that concentration is 1mg/ml
Solution, then take in 0.5ml flunarizine solution measuring bottles, with methanol constant volume to 100ml, it is molten to obtain flunarizine reference substance
Liquid.
In the step (2), according to auxiliary improvement of memory class Chinese medicine preparation and the formulation difference collocation method of health food
Can be otherwise varied, it is specific as follows：
The collocation method of liquid preparation：Precision draws a suitable oral dose, puts in 50ml measuring bottles, adds 20ml
50% methanol aqueous solution, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, let cool, be settled to 50% methanol aqueous solution
Scale, shake up, take 1ml solution to be diluted with water 10 times, it is stand-by as need testing solution.
The collocation method of solid pharmaceutical preparation：Take solid pharmaceutical preparation test sample finely ground, precision weighs equivalent to one time oral dose, puts
In 100ml conical flasks, precision adds the methanol aqueous solutions of 50ml 50%, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated
15min, let cool, supply weight with 50% methanol aqueous solution, take 1ml supernatants to be diluted with water 10 times, treated as need testing solution
With.
The collocation method of soft capsule preparation：Precision weighs equivalent to one time oral dose soft capsule, puts 100ml conical flasks
In, precision adds the methanol aqueous solutions of 50ml 50%, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, lets cool,
Weight is supplied with 50% methanol aqueous solution, 4 DEG C of refrigerators is placed in and places 2.5h, solution is transferred to centrifuge tube, 4000rmin-1From
Heart 5min, 1ml supernatants are taken to be diluted with water 10 times, it is stand-by as need testing solution.
In the step (2), purification process is as follows：Precision measures need testing solution 1ml with 1mlmin-1Flow velocity passes through work
C18-SPE posts after change, eluted with the methanol-waters of 2ml 50%, merge efflux and eluent, and be settled to 5ml, with 0.22 μm
Organic membrane filtration, produces testing sample solution.
Compared with prior art, the invention has the advantages that：
This hair name provides the LC-MS detection of flunarizine in auxiliary improvement of memory class Chinese medicine preparation and health food
Method, this method are detected by the way of multiple-reaction monitoring, interference less, high sensitivity, testing result it is accurate.
Embodiment
Embodiment 1
(1) reference substance solution is prepared：The dissolving of flunarizine reference substance methanol is taken to be configured to the fluorine osmanthus that concentration is 1mg/ml
Sharp piperazine solution, then take in 1ml flunarizine solution measuring bottles, with methanol constant volume to 100ml, it is molten to obtain flunarizine reference substance
Liquid.
(2) testing sample solution is prepared：The collocation method of liquid preparation：Precision draws a suitable oral dose, puts
In 50ml measuring bottles, the methanol aqueous solutions of 20ml 50% are added, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, let cool, use
50% methanol aqueous solution is settled to scale, shakes up, and takes 1ml solution to be diluted with water 10 times, stand-by as need testing solution.
The collocation method of solid pharmaceutical preparation：Take solid pharmaceutical preparation test sample finely ground, precision weighs equivalent to one time oral dose, puts
In 100ml conical flasks, precision adds the methanol aqueous solutions of 50ml 50%, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated
15min, let cool, supply weight with 50% methanol aqueous solution, take 1ml supernatants to be diluted with water 10 times, treated as need testing solution
With.
The collocation method of soft capsule preparation：Precision weighs equivalent to one time oral dose soft capsule, puts 100ml conical flasks
In, precision adds the methanol aqueous solutions of 50ml 50%, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, lets cool,
Weight is supplied with 50% methanol aqueous solution, 4 DEG C of refrigerators is placed in and places 2.5h, solution is transferred to centrifuge tube, 4000rmin-1From
Heart 5min, 1ml supernatants are taken to be diluted with water 10 times, it is stand-by as need testing solution.
Purification process is as follows：Precision measures need testing solution 1ml with 1mlmin-1Flow velocity passes through the C18-SPE after activation
Post, eluted with the methanol-waters of 2ml 50%, merge efflux and eluent, and be settled to 5ml, with 0.22 μm of organic membrane filtration,
Produce testing sample solution.
(3) reference substance solution and testing sample solution upper liquid matter combined instrument is taken to carry out the flunarizine in need testing solution
Qualitative, quantitative determines, wherein,
Chromatographic condition：3.0mm × 100mm, 1.8 μm, Eclipse XDB C18Chromatographic column, flow velocity：0.30ml·min-1,
Column temperature：40 DEG C, sample size:1μl；ESI holotypes：Mobile phase A is 0.1% formic acid solution, and Mobile phase B is methanol；Gradient elution
Program：0~2min, 92%A, 10%B；2~10min, 92%~8%A, 8%~92%B；10~13min, 10%A, 92%
B；2min is balanced under 90%A, 10%B；ESI negative modes：Mobile phase A is water, and Mobile phase B is acetonitrile；Gradient elution program:0
~0.5min, 85%A, 15%B；0.5~3min, 85%~10%A, 15%~90%B；3~5min, 15%A, 85%B；
2min is balanced under 85%A, 15%B；
Mass Spectrometry Conditions：Electric spray ion source (ESI), negative ions pattern, multiple-reaction monitoring (MRM) scan mode：M/z is
405.2/200.1, fragmentation voltage 100V, impact energy 50V, retention time 8.5min, temperature degree is dried：360 DEG C, atomizer pressure
Power：40Psi, dry gas stream speed：10L·min–1。
(4) linear relationship is investigated：Precision draws 5 μ gml-1Flunarizine reference substance solution 20,50,80,120,160,
200 μ l, put in 6 10ml measuring bottles, add mobile phase to be settled to scale, shake up, produce the mixing contrast solution of 6 concentration levels,
Respectively 10,25,40,60,80,100ngml-1, 1 μ l are respectively taken, are analyzed by the LC-MS condition sample introduction of above-mentioned steps (3),
Parallel determination 2 times, with peak area (Y) to mass concentration (X, ngml-1) linear regression is carried out, obtain regression equation Y=
55.88X-125.50 with correlation coefficient r=0.9970, show flunarizine in 10.84~108.2ngml-1In the range of it is linear
Relation is good.
(5) after test limit progressively dilutes flunarizine reference substance solution, surveyed by the LC-MS condition of above-mentioned steps (3)
Fixed, the detection that each chemical composition is calculated by S/N=3 is limited to 3ngml-1。
(6) precision test：Flunarizine reference substance solution is taken, concentration 100ng/ml, is joined using the liquid matter of step (3)
With condition sample introduction 6 times, as a result the RSD of the peak area of flunarizine is less than 2.5% (n=6), illustrates that instrument precision is good.
(7) stability test：Take flunarizine reference substance solution, concentration 100ng/ml, respectively in 0,1,8,12 and 24h
According to the LC-MS condition sample introduction such as step (3), stability of solution is investigated, the results showed that, flunarizine is stable in 24h.
(8) average recovery is tested:Take 1 flunarizine blank sample, add the μ g of flunarizine reference substance about 50, by treating
Test sample product solution manufacturing method it is parallel prepare 6 parts of testing sample solutions, by above-mentioned steps (3) LC-MS condition sample introduction and survey
Determine the rate of recovery.As a result show that the average recovery scope of flunarizine is less than 5% (n=6) for 96%~105%, RSD.
(9) sample determines：Take oral liquid 4 batches, soft capsule 6 batches altogether, hard shell capsules 3 batches and 2 batches, tablet, prepared by step (2)
Testing sample solution, by above-mentioned steps (3) liquid matter condition sample detection, as a result flunarizine does not detect in 15 batches of samples.
The present invention can be summarized with others without prejudice to the concrete form of the spirit or essential characteristics of the present invention.The present invention's
The embodiment above can only all be considered the description of the invention rather than limitation, therefore every substantial technological according to the present invention
Any subtle modifications, equivalent variations and modifications made to above example, are belonged in the range of technical solution of the present invention.
Claims (6)
1. a kind of method of flunarizine in LC-MS detection Chinese patent drug and health food, it is characterized in that, comprise the following steps：
(1) reference substance solution is prepared：Take flunarizine reference substance that reference substance solution is made with methanol；
(2) testing sample solution is prepared：Take auxiliary improvement of memory class Chinese medicine preparation and health food to be extracted using methanol, and will carry
Take resulting solution is purified to obtain testing sample solution；
(3) reference substance solution and testing sample solution upper liquid matter combined instrument is taken to carry out the flunarizine in need testing solution qualitative
Quantitative determination, wherein,
Chromatographic condition：3.0mm × 100mm, 1.8 μm, Eclipse XDB C18Chromatographic column, flow velocity：0.30ml·min-1, column temperature：
40 DEG C, sample size:1μl；ESI holotypes：Mobile phase A is 0.1% formic acid solution, and Mobile phase B is methanol；Gradient elution program：0
~2min, 92%A, 10%B；2~10min, 92%~8%A, 8%~92%B；10~13min, 10%A, 92%B；
2min is balanced under 90%A, 10%B；ESI negative modes：Mobile phase A is water, and Mobile phase B is acetonitrile；Gradient elution program:0~
0.5min, 85%A, 15%B；0.5~3min, 85%~10%A, 15%~90%B；3~5min, 15%A, 85%B；
2min is balanced under 85%A, 15%B；
Mass Spectrometry Conditions：Electric spray ion source, negative ions pattern, multiple-reaction monitoring scan mode：M/z is 405.2/200.1, broken
Voltage 100V, impact energy 50V, retention time 8.5min are split, dries temperature degree：360 DEG C, nebulizer pressure：40Psi, dry gas
Flow velocity：10L·min–1。
2. the method for flunarizine, its feature in LC-MS detection Chinese patent drug according to claim 1 and health food
It is in the step (1), to take the dissolving of flunarizine reference substance methanol to be configured to the flunarizine solution that concentration is 1mg/ml,
Then take in 0.5ml flunarizine solution measuring bottles, with methanol constant volume to 100ml, obtain flunarizine reference substance solution.
3. the method for flunarizine, its feature in LC-MS detection Chinese patent drug according to claim 1 and health food
It is, in the step (2), the testing sample solution collocation method of liquid preparation：Precision draws a suitable oral dose, puts
In 50ml measuring bottles, the methanol aqueous solutions of 20ml 50% are added, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, let cool, use
50% methanol aqueous solution is settled to scale, shakes up, and takes 1ml solution to be diluted with water 10 times, stand-by as need testing solution.
4. the method for flunarizine, its feature in LC-MS detection Chinese patent drug according to claim 1 and health food
It is, in the step (2), the testing sample solution collocation method of solid pharmaceutical preparation：Take that solid pharmaceutical preparation test sample is finely ground, and precision weighs
Equivalent to one time oral dose, puts in 100ml conical flasks, and precision adds the methanol aqueous solutions of 50ml 50%, weighs, in 1130W,
It is lower under the conditions of 37kHz to be ultrasonically treated 15min, let cool, weight is supplied with 50% methanol aqueous solution, take 1ml supernatants to be diluted with water
It is 10 times, stand-by as need testing solution.
5. the method for flunarizine, its feature in LC-MS detection Chinese patent drug according to claim 1 and health food
It is, in the step (2), the testing sample solution collocation method of soft capsule preparation：Precision weighs equivalent to one time oral dose
Soft capsule, put in 100ml conical flasks, precision adds the methanol aqueous solutions of 50ml 50%, weighs, under the conditions of the 1130W, 37kHz under
15min is ultrasonically treated, lets cool, weight is supplied with 50% methanol aqueous solution, 4 DEG C of refrigerators is placed in and places 2.5h, solution is transferred to
Centrifuge tube, 4000rmin-15min is centrifuged, takes 1ml supernatants to be diluted with water 10 times, it is stand-by as need testing solution.
6. the side of flunarizine in the LC-MS detection Chinese patent drug and health food according to claim any one of 1-5
Method, it is characterized in that, in the step (2), purification process is as follows：Precision measures need testing solution 1ml with 1mlmin-1Flow velocity leads to
C18-SPE posts after overactivation, eluted with the methanol-waters of 2ml 50%, merge efflux and eluent, and be settled to 5ml, used
0.22 μm of organic membrane filtration, produces testing sample solution.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711366205.1A CN107884500A (en) | 2017-12-18 | 2017-12-18 | The method that LC-MS detects flunarizine in Chinese patent drug and health food |
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| CN201711366205.1A CN107884500A (en) | 2017-12-18 | 2017-12-18 | The method that LC-MS detects flunarizine in Chinese patent drug and health food |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110967421A (en) * | 2019-11-15 | 2020-04-07 | 正大青春宝药业有限公司 | Method for detecting related substances of flunarizine hydrochloride preparation |
| CN117030867A (en) * | 2023-05-12 | 2023-11-10 | 石家庄市华新药业有限责任公司 | Method for detecting various genotoxic impurities in flunarizine hydrochloride capsules |
-
2017
- 2017-12-18 CN CN201711366205.1A patent/CN107884500A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110967421A (en) * | 2019-11-15 | 2020-04-07 | 正大青春宝药业有限公司 | Method for detecting related substances of flunarizine hydrochloride preparation |
| CN110967421B (en) * | 2019-11-15 | 2022-04-12 | 正大青春宝药业有限公司 | Method for detecting related substances of flunarizine hydrochloride preparation |
| CN117030867A (en) * | 2023-05-12 | 2023-11-10 | 石家庄市华新药业有限责任公司 | Method for detecting various genotoxic impurities in flunarizine hydrochloride capsules |
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Application publication date: 20180406 |