CN108107128A - The method that LC-MS detects donepezil in Chinese patent drug and health food - Google Patents
The method that LC-MS detects donepezil in Chinese patent drug and health food Download PDFInfo
- Publication number
- CN108107128A CN108107128A CN201711366243.7A CN201711366243A CN108107128A CN 108107128 A CN108107128 A CN 108107128A CN 201711366243 A CN201711366243 A CN 201711366243A CN 108107128 A CN108107128 A CN 108107128A
- Authority
- CN
- China
- Prior art keywords
- solution
- donepezil
- methanol
- health food
- reference substance
- 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
Classifications
-
- 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
Abstract
The invention discloses the methods of donepezil in a kind of LC-MS detection Chinese patent drug and health food, comprise the following steps：(1) reference substance solution is prepared：Take donepezil 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 acquired 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 donepezil in test 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 donepezil more particularly to a kind of LC-MS detection Chinese patent drugs and health food
The method of middle donepezil.
Background technology
Donepezil has nootropic effect, but it is mainly used for 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 generate loss of appetite, Nausea and vomiting, dry, headache, palpitaition, dermatitis
Wait side effects.
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.However some illegal retailers are possessed with a lust for gain, it is non-in health products
Method adds chemicals, is then illegally publicized, 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, stealthily illegally adds in western medicine composition in Chinese patent drug and health food.At present, auxiliary improvement of memory class health food may be non-
Method adds drug, including donepezil, 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 donepezil in auxiliary improvement of memory class Chinese medicine preparation and health food
It is detected, for preventing and supervising auxiliary improvement of memory class Chinese patent drug and health food enters 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 donepezil it is fast
Fast screening method.
The content of the invention
The method that the purpose of the present invention is intended to provide donepezil 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 donepezil, comprises the following steps：
(1) reference substance solution is prepared：Take donepezil 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 acquired 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 donepezil in test solution
Qualitative, quantitative measures, 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
380.2/287.1, fragmentation voltage 155V, impact energy 25V, retention time 6.8min, dry temperature degree:360 DEG C, atomizer pressure
Power：40Psi, dry gas stream speed：10L·min–1。
In the step (1), the dissolving of donepezil reference substance methanol is taken to be configured to the donepezil that concentration is 1mg/ml
Then solution takes in 0.5ml donepezil solution measuring bottles, with methanol constant volume to 100ml, it is molten to obtain donepezil reference substance
Liquid.
In the step (2), according to auxiliary improvement of memory class Chinese medicine preparation and the dosage form 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 in 20ml
50% methanol aqueous solution, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, it lets cool, is settled to 50% methanol aqueous solution
Scale shakes up, and 1ml solution is taken to be diluted with water 10 times, for use as test solution.
The collocation method of solid pharmaceutical preparation：Take solid pharmaceutical preparation test sample finely ground, precision, which weighs, is equivalent to an oral dose, puts
In 100ml conical flasks, precision adds in 50% methanol aqueous solutions of 50ml, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated
15min is let cool, and supplies weight with 50% methanol aqueous solution, 1ml supernatants is taken to be diluted with water 10 times, are treated as test solution
With.
The collocation method of soft capsule preparation：Precision, which weighs, is equivalent to an oral dose soft capsule, puts 100ml conical flasks
In, precision adds in 50% methanol aqueous solutions of 50ml, 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 takes 1ml supernatants to be diluted with water 10 times, for use as test solution.
In the step (2), purification process is as follows：Precision measures test solution 1ml with 1mlmin-1Flow velocity passes through work
C18-SPE columns after change are eluted with 50% methanol-waters of 2ml, merge efflux and eluent, and are settled to 5ml, with 0.22 μm
Organic membrane filtration is to get testing sample solution.
Compared with prior art, the invention has the advantages that：
This hair name provides the LC-MS detection of donepezil 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.
Specific embodiment
Embodiment 1
(1) reference substance solution is prepared：Take donepezil reference substance methanol dissolving be configured to concentration be 1mg/ml it is more how
Then the neat solution of piperazine takes in 1ml donepezil solution measuring bottles, with methanol constant volume to 100ml, it is molten to obtain donepezil 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, 50% methanol aqueous solutions of 20ml are added in, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, it lets cool, uses
50% methanol aqueous solution is settled to scale, shakes up, and 1ml solution is taken to be diluted with water 10 times, for use as test solution.
The collocation method of solid pharmaceutical preparation：Take solid pharmaceutical preparation test sample finely ground, precision, which weighs, is equivalent to an oral dose, puts
In 100ml conical flasks, precision adds in 50% methanol aqueous solutions of 50ml, weighs, lower under the conditions of 1130W, 37kHz to be ultrasonically treated
15min is let cool, and supplies weight with 50% methanol aqueous solution, 1ml supernatants is taken to be diluted with water 10 times, are treated as test solution
With.
The collocation method of soft capsule preparation：Precision, which weighs, is equivalent to an oral dose soft capsule, puts 100ml conical flasks
In, precision adds in 50% methanol aqueous solutions of 50ml, 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 takes 1ml supernatants to be diluted with water 10 times, for use as test solution.
Purification process is as follows：Precision measures test solution 1ml with 1mlmin-1Flow velocity passes through the C18-SPE after activation
Column is eluted with 50% methanol-waters of 2ml, merges efflux and eluent, and is settled to 5ml, with 0.22 μm of organic membrane filtration,
Up to testing sample solution.
(3) reference substance solution and testing sample solution upper liquid matter combined instrument is taken to carry out the donepezil in test solution
Qualitative, quantitative measures, 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
380.2/287.1, fragmentation voltage 155V, impact energy 25V, retention time 6.8min, dry temperature degree：360 DEG C, atomizer pressure
Power：40Psi, dry gas stream speed：10L·min–1。
(4) linear relationship is investigated：Precision draws 5 μ gml-1Donepezil reference substance solution 20,50,80,120,160,
200 μ l put in 6 10ml measuring bottles, mobile phase are added to be settled to scale, shake up to get the mixing contrast solution of 6 concentration levels,
Respectively 10,25,40,60,80,100ngml-1, 1 μ l are respectively taken, by the LC-MS condition of above-mentioned steps (3), sample introduction is analyzed,
Parallel determination 2 times, with peak area (Y) to mass concentration (X, ngml-1) linear regression is carried out, obtain regression equation Y=
60.68X-68.55 and correlation coefficient r=0.9995 show donepezil in 10.81~108.2ngml-1In the range of linearly close
System is good.
(5) after detection limit progressively dilutes donepezil 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：Donepezil 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 donepezil is less than 2.5% (n=6), illustrates that instrument precision is good.
(7) stability test：Take donepezil reference substance solution, concentration 100ng/ml, respectively 0,1,8,12 and for 24 hours
According to the LC-MS condition sample introduction such as step (3), stability of solution is investigated, the results showed that, donepezil is stablized in 12h.
(8) sample recovery rate is tested:It takes 1 donepezil blank sample, adds in about 50 μ g of donepezil reference substance, by treating
Sample 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.The sample recovery rate scope of the results show donepezil is less than 5% (n=6) for 93%~101%, RSD.
(9) sample measures：Take oral liquid 4 batches, soft capsule 6 batches altogether, hard shell capsules 3 batches and 2 batches, tablet are prepared by step (2)
Testing sample solution, by above-mentioned steps (3) liquid matter condition sample detection, as a result donepezil 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 invention
To any subtle modifications, equivalent variations and modifications that above example is made, belong in the range of technical solution of the present invention.
Claims (6)
1. a kind of method of donepezil 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 donepezil 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 will be carried
Take acquired 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 donepezil in test 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 380.2/287.1, broken
Split voltage 155V, impact energy 25V, retention time 6.8min, dry temperature degree：360 DEG C, nebulizer pressure：40Psi, dry gas
Flow velocity：10L·min–1。
2. the method for donepezil, feature in LC-MS detection Chinese patent drug according to claim 1 and health food
It is in the step (1), the dissolving of donepezil reference substance methanol to be taken to be configured to the donepezil solution that concentration is 1mg/ml,
Then take in 0.5ml donepezil solution measuring bottles, with methanol constant volume to 100ml, obtain donepezil reference substance solution.
3. the method for donepezil, 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, 50% methanol aqueous solutions of 20ml are added in, it is lower under the conditions of 1130W, 37kHz to be ultrasonically treated 15min, it lets cool, uses
50% methanol aqueous solution is settled to scale, shakes up, and 1ml solution is taken to be diluted with water 10 times, for use as test solution.
4. the method for donepezil, 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
An oral dose is equivalent to, is put in 100ml conical flasks, precision adds in 50% methanol aqueous solutions of 50ml, weighs, in 1130W,
It is lower under the conditions of 37kHz to be ultrasonically treated 15min, it lets cool, weight is supplied with 50% methanol aqueous solution, 1ml supernatants is taken to be diluted with water
It is 10 times, for use as test solution.
5. the method for donepezil, 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, which weighs, is equivalent to an oral dose
Soft capsule is put in 100ml conical flasks, and precision adds in 50% methanol aqueous solutions of 50ml, 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, 1ml supernatants is taken to be diluted with water 10 times, it is for use as test solution.
6. the side of donepezil in Chinese patent drug and health food is detected according to claim 1-5 any one of them LC-MS
Method, it is characterized in that, in the step (2), purification process is as follows：Precision measures test solution 1ml with 1mlmin-1Flow velocity leads to
C18-SPE columns after overactivation are eluted with 50% methanol-waters of 2ml, merge efflux and eluent, and are settled to 5ml, are used
0.22 μm of organic membrane filtration is to get testing sample solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711366243.7A CN108107128A (en) | 2017-12-18 | 2017-12-18 | The method that LC-MS detects donepezil in Chinese patent drug and health food |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711366243.7A CN108107128A (en) | 2017-12-18 | 2017-12-18 | The method that LC-MS detects donepezil in Chinese patent drug and health food |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108107128A true CN108107128A (en) | 2018-06-01 |
Family
ID=62209969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711366243.7A Pending CN108107128A (en) | 2017-12-18 | 2017-12-18 | The method that LC-MS detects donepezil in Chinese patent drug and health food |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108107128A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109946364A (en) * | 2019-04-10 | 2019-06-28 | 南方医科大学珠江医院 | The method for detecting donepezil blood concentration |
-
2017
- 2017-12-18 CN CN201711366243.7A patent/CN108107128A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109946364A (en) * | 2019-04-10 | 2019-06-28 | 南方医科大学珠江医院 | The method for detecting donepezil blood concentration |
| CN109946364B (en) * | 2019-04-10 | 2021-03-16 | 南方医科大学珠江医院 | Method for detecting blood concentration of donepezil |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108051534A (en) | A kind of method of the 132 kinds of chemicalses illegally added in rapid screening Chinese patent drug and health products | |
| Cui et al. | Simultaneous determination of ten flavonoids of crude and wine‐processed Radix Scutellariae aqueous extracts in rat plasma by UPLC‐ESI‐MS/MS and its application to a comparative pharmacokinetic study | |
| US8319194B2 (en) | Drug detection equipment | |
| CN105651924B (en) | The detection method of hormone in blood | |
| Sun et al. | Simultaneous determination of four flavonoids and one phenolic acid in rat plasma by LC–MS/MS and its application to a pharmacokinetic study after oral administration of the Herba Desmodii Styracifolii extract | |
| CN107741464A (en) | 22 kinds of illegal detection methods for adding class drug residue of calming the nerves in health products | |
| CN108152402A (en) | The method that LC-MS detects Edaravone in Chinese patent drug and health food | |
| CN107884500A (en) | The method that LC-MS detects flunarizine in Chinese patent drug and health food | |
| EP3954371A1 (en) | Anti-acetylcholinesterase active composition in caulis mahoniae and screening method therefor and application thereof | |
| Ding et al. | Determination of palonosetron in human plasma by liquid chromatography–electrospray ionization-mass spectrometry | |
| CN108107128A (en) | The method that LC-MS detects donepezil in Chinese patent drug and health food | |
| Wen et al. | A sensitive liquid chromatography–electrospray ionization–mass spectrometry method for the simultaneous determination of pentoxyverine citrate and guaifenesin in human plasma—application to pharmacokinetic and bioequivalence studies | |
| CN108120774A (en) | The method that LC-MS detects Nimodipine in Chinese patent drug and health food | |
| CN105301127B (en) | A kind of Ribavirin pharmaceutical composition and its related substance detecting method | |
| CN107884501A (en) | The method that LC-MS detects Betahistine in Chinese patent drug and health food | |
| CN108107139A (en) | The method that LC-MS detects aniracetam in Chinese patent drug and health food | |
| CN108107148A (en) | The method that LC-MS detects huperzine in Chinese patent drug and health food | |
| CN107991413A (en) | The method that LC-MS detects galanthamine in Chinese patent drug and health food | |
| CN107957468A (en) | The method that LC-MS detects Flumazenil in Chinese patent drug and health food | |
| CN108169358A (en) | The method that LC-MS detects diethylstilbestrol in Chinese patent drug and health food | |
| CN107957469A (en) | The method that LC-MS detects Piracetam in Chinese patent drug and health food | |
| CN107831239A (en) | The method that LC-MS detects almitrine in Chinese patent drug and health food | |
| CN107957470A (en) | The method that LC-MS detects caffeine in Chinese patent drug and health food | |
| CN108120793A (en) | The method that LC-MS detects naproxen in Chinese patent drug and health food | |
| CN108152403A (en) | The method that LC-MS detects estriol in Chinese patent drug and health food |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180601 |
|
| WD01 | Invention patent application deemed withdrawn after publication |