CN108152422A - The analysis method that drug content measures in a kind of amantadine hydrochloride solid pharmaceutical preparation - Google Patents
The analysis method that drug content measures in a kind of amantadine hydrochloride solid pharmaceutical preparation Download PDFInfo
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- CN108152422A CN108152422A CN201810092298.1A CN201810092298A CN108152422A CN 108152422 A CN108152422 A CN 108152422A CN 201810092298 A CN201810092298 A CN 201810092298A CN 108152422 A CN108152422 A CN 108152422A
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- amantadine hydrochloride
- solid pharmaceutical
- pharmaceutical preparation
- drug content
- analysis method
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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
Abstract
The invention discloses the analysis methods that drug content in a kind of amantadine hydrochloride solid pharmaceutical preparation measures, and using the capillary column that fixer is 5% phenyl, 95% methyl polysiloxane as chromatographic column, are measured using gas-chromatography (GC) method.Compared to more existing detection technique potentiometric titration to the assay method of drug content in amantadine hydrochloride solid pharmaceutical preparation, through methodology validation, analysis method of the present invention has many advantages, such as error that is efficient, quick, accurate, and reducing manual operation.
Description
Technical field
The present invention relates to main ingredients in Pharmaceutical Analysis detection technique field more particularly to a kind of amantadine hydrochloride solid pharmaceutical preparation
The analysis method of assay.
Background technology
Amantadine hydrochloride (Amantadine Hydrochloride, 8-38) is a kind of symmetrical three cyclic amine, can be with
Virus is inhibited to penetrate host cell, and influences the shelling of virus, inhibits its breeding, serves and treats and prevents viral infection.
Amantadine antiviral spectrum is relatively narrow, is mainly used for the prevention of Asia A type influenzas, for Type B influenza virus and rubella virus, fiber crops
Exanthema virus, mumps virus and herpes simplex infections are invalid.Because after oral absorption can by blood-brain barrier,
Central nervous system toxicity can be caused.It clinically can effectively prevent and treat the infection of various influenza As.
The influenza pandemic phase makees preventive medicine using this product, and protective rate, to having sent out patient, is such as administered in 48h, can have up to 50%~79%
Effect ground treatment respiratory symptom caused by influenza A.
Version pharmacopeia in 2015 is measured using potentiometric titration for amantadine hydrochloride drug content at present, tablet contains
It is also potentiometric titration to measure fixed 2015 version pharmacopeia and use.However this detection method has jumping unobvious in the analysis process
The defects of, it is larger there are human factor because requiring to be unable to machine titration, raw material, intermediate and finished product content is often caused to miss
The defects of poor.
Invention content
The present invention to solve in the prior art, survey caused by manual operation factor is larger by raw material, intermediate and finished product content
Determine error, propose the analysis method that drug content measures in a kind of amantadine hydrochloride solid pharmaceutical preparation.
The analysis method that drug content of the present invention measures is using gas-chromatography (GC) method, with -95% methyl polysilicon of 5% phenyl
Oxygen alkane (or polarity is similar) is that the capillary column of fixer is chromatographic column, effectively reduces the error of manual operation.
To achieve the above object, the present invention uses following technical scheme：
The present invention provides the analysis method that drug content measures in a kind of amantadine hydrochloride solid pharmaceutical preparation, using fixer as
The capillary column of -95% methyl polysiloxane of 5% phenyl is chromatographic column, is measured using gas-chromatography (GC) method.
Further, it is described in the analysis method that drug content measures in the amantadine hydrochloride solid pharmaceutical preparation
The chromatographic condition and system suitability of gas-chromatography (GC) method are as follows：
Chromatographic condition：It is the capillary column of -95% methyl polysiloxane of 5% phenyl (or polarity is similar) for color using fixer
Column is composed, initial temperature is 70 DEG C, is maintained 5 minutes, is warming up to 250 DEG C with 10 DEG C per minute of rate, maintains 17 minutes, injection port
Temperature is 220 DEG C, and detector temperature is 300 DEG C；
System suitability：Amantadine hydrochloride and each 5mg of adamantane reference substance are weighed respectively, are placed in 10ml measuring bottles, are added
Chloroform dissolves, until scale, shakes up, both；It is required that amantadine hydrochloride peak and the separating degree at adamantane peak are more than 20, Buddha's warrior attendant
The signal-to-noise ratio of alkanamine peak height should be greater than 30.
It is further preferred that in the analysis method that drug content measures in the amantadine hydrochloride solid pharmaceutical preparation,
The assay method of gas-chromatography (GC) method is as follows：
(1) preparation of test solution：Precision weighs Symmetrel, is equivalent to amantadine hydrochloride 75mg,
It is weighed, put in 50ml measuring bottles, chloroform added to dissolve and is diluted to scale, shake up to get；
(2) preparation of reference substance solution：Take amantadine hydrochloride reference substance appropriate, it is accurately weighed, chloroform is added to prepare
Into every 1ml saliferous symmetrel 1.5mg solution to get；
(3) it is accurate to measure test solution and each 2 μ l injections gas chromatograph of reference substance solution, chromatogram is recorded, is calculated
Obtain amantadine hydrochloride content.
The present invention compared with prior art, is had the following technical effect that using above-mentioned technical proposal：
In amantadine hydrochloride solid pharmaceutical preparation provided by the invention drug content measure analysis method, using fixer as
The capillary column of -95% methyl polysiloxane of 5% phenyl is chromatographic column, is measured using gas-chromatography (GC) method；Through method
Verification is learned, compared to more existing detection technique potentiometric titration to the assay method of this product content, is had efficiently, fast, accurately
The advantages that, and reduce the error of manual operation；Can be to improve the formula of amantadine hydrochloride solid pharmaceutical preparation and its to medicine simultaneously
The assay of adamantane provides important references in product.
Description of the drawings
Fig. 1 is the HPLC collection of illustrative plates of reference substance solution；
Fig. 2 is adamantane linear relationship chart and linear diagram.
Specific embodiment
The present invention is described in more detail below by specific embodiment, for a better understanding of the present invention,
But following embodiments are not intended to limit the scope of the invention.
The measure of drug content in embodiment amantadine hydrochloride solid pharmaceutical preparation
(1) reagent is shown in Table 1：
1 reagent source of table
(2) chromatographic condition of gas-chromatography (GC) method and system suitability are as follows：
Chromatographic condition：Using the capillary column that fixer is -95% methyl polysiloxane of 5% phenyl as chromatographic column, starting temperature
It is 70 DEG C to spend, and is maintained 5 minutes, is warming up to 250 DEG C with 10 DEG C per minute of rate, maintains 17 minutes, injector temperature 220
DEG C, detector temperature is 300 DEG C；
System suitability：Amantadine hydrochloride and each 5mg of adamantane reference substance are weighed respectively, are placed in 10ml measuring bottles, are added
Chloroform dissolves, until scale, shakes up, both；It is required that amantadine hydrochloride peak and the separating degree at adamantane peak are more than 20, Buddha's warrior attendant
The signal-to-noise ratio of alkanamine peak height should be greater than 30.
(3) assay method of gas-chromatography (GC) method：
(1) preparation of test solution：Precision weighs Symmetrel, is equivalent to amantadine hydrochloride 75mg,
It is weighed, put in 50ml measuring bottles, chloroform added to dissolve and is diluted to scale, shake up to get；
(2) preparation of reference substance solution：Take amantadine hydrochloride reference substance appropriate, it is accurately weighed, chloroform is added to prepare
Into every 1ml saliferous symmetrel 1.5mg solution to get；
(3) it is accurate to measure test solution and each 2 μ l injections gas chromatograph of reference substance solution, chromatogram is recorded, is calculated
Obtain adamantane content.
Method validation is the science for ensuring content assaying method of the present invention, reasonable, feasible, and inventor has carried out a series of
Experimental study and investigation.Chromatographic condition for the assay method of drug content in amantadine hydrochloride solid pharmaceutical preparation of the present invention below
After determining, verify that it measures the experiment of effect.
1st, detection limit and quantitative limit experiment
1.1 evaluation criterion
Detection limit evaluation criterion：Signal-to-noise ratio is 3:1, relative standard deviation is not more than 10.0%.
Quantitative limit evaluation criterion：Signal-to-noise ratio about 10:1, relative standard deviation is not more than 10.0%.
1.2 prepare detection limit test liquid and quantitative limit test liquid
Quantitative limit test liquid：Precision measures reference substance solution 1ml and puts in 100ml measuring bottles, and chloroform is diluted to scale, shakes
It is even, solution S is obtained, precision measures S solution 1ml and puts in 10ml measuring bottles, and chloroform is diluted to scale, shakes up.
Detection limit test liquid：Precision measures quantitative limit and is put in 10ml measuring bottles for examination 3ml, and chloroform is diluted to scale, shakes
It is even.
1.3 assay method
A, operation is protected from light, precision measures above-mentioned detection limit test liquid 2ul, with signal-to-noise ratio 3:Gas chromatograph is injected when 1, really
The fixed a concentration of minimal detectable concentration by minimal detectable concentration continuous sample introduction 6 times, is measured by embodiment chromatographic condition, remembered
Record the peak area at hydrochloric acid adamantane peak in chromatogram, the results showed that：The RSD values of peak area are 7.54% (being shown in Table 2), meet detection
Limit evaluation criterion.
The detection limit result of table 2
B, operation is protected from light, precision measures above-mentioned each 2ul of quantitative limit test liquid, with signal-to-noise ratio 10:High-efficient liquid phase color is injected when 1
Spectrometer determines a concentration of quantitative limit concentration, and minimal detectable concentration continuous sample introduction 6 times is surveyed by embodiment chromatographic condition
It is fixed, record the peak area at hydrochloric acid adamantane peak in chromatogram, the results showed that：The RSD values of peak area are 2.89% (being shown in Table 3), are accorded with
Close limitation property evaluation criterion.
3 quantitative limit result of table
2nd, linear test
The preparation of 2.1 test liquids
A. quantitative limit solution.
B. S solution 5ml is taken to put in 10ml measuring bottles, chloroform is diluted to scale, shakes up.
C. S solution 8ml is taken to put in 10ml measuring bottles, chloroform is diluted to scale, shakes up.
D. S solution is taken.
E. contrast solution 1.5ml is taken to put in 100ml measuring bottles, chloroform is diluted to scale, shakes up.
F. contrast solution 1.8ml is taken to put in 100ml measuring bottles, chloroform is diluted to scale, shakes up
It is accurate respectively to measure each 2ul injections gas chromatograph of above-mentioned test liquid A, B, C, D, E, F, by embodiment chromatographic condition
It is measured, records chromatogram, calculate related coefficient and linear equation (being shown in Table 4), be with the amount (ug/mL) of adamantane test liquid
Abscissa (X), peak area are ordinate (Y), draw standard curve (see Fig. 2), and the regression equation for obtaining adamantane is y=
0.6911x-0.00771, the results showed that：The content of hydrochloric acid adamantane, in good linear relationship, can meet measure with peak area
It is required that.
4 related coefficient of table and linear equation
3rd, accuracy, precision, specificity experiment
Evaluation criterion：The rate of recovery 98.0%~102.0%；Auxiliary material interference≤2.0%；RSD≤2.0%.
The preparation of comparison liquid：Precision weighs amantadine hydrochloride reference substance 0.07526g, puts in 50ml measuring bottles, chloroform
Dissolving, be diluted to scale, shake up to get.
Test liquid：Precision weighs amantadine hydrochloride raw material 60mg, 75mg, 90mg (each three parts), puts in 50ml measuring bottles, respectively
Blank auxiliary about 102mg is added in, chloroform dissolving is diluted to scale, shakes up.
Material liquid：Precision weighs amantadine hydrochloride raw material 75mg, puts in 50ml measuring bottles, and chloroform dissolving is diluted to
Scale shakes up.
Blank auxiliary liquid：Precision weighs blank auxiliary about 102mg, puts in 50ml measuring bottles, and chloroform dissolving is diluted to quarter
Degree, shakes up.
Each 2ul injections gas chromatograph of above-mentioned each solution is taken, record chromatogram is measured by embodiment chromatographic condition, remembers
Record the peak area at hydrochloric acid adamantane peak in chromatogram, the results showed that：The average recovery rate of peak area is that 100%, RSD9 is
0.34%, show that the accuracy of this method is high, high-specificity, instrument precision is good (being shown in Table 5).
5 accuracy of table, precision, specificity experimental result
As can be seen that this method accuracy, precision, specificity meet from above-mentioned each summary sheet and each detection data
Regulation, average recovery rate 100%, RSD9 0.34%；Linearly dependent coefficient r=1.000；Comply with standard.This method can
Can be to improve amantadine hydrochloride to consolidate to apply to measure the practice examining of adamantane content in amantadine hydrochloride solid pharmaceutical preparation
The formula of body preparation and its assay offer important references to hydrochloric acid adamantane in drug.
Specific embodiments of the present invention are described in detail above, but it is intended only as example, it is of the invention and unlimited
It is formed on particular embodiments described above.To those skilled in the art, it is any to the equivalent modifications that carry out of the present invention and
It substitutes also all among scope of the invention.Therefore, the impartial conversion made without departing from the spirit and scope of the invention and
Modification, all should be contained within the scope of the invention.
Claims (3)
1. in a kind of amantadine hydrochloride solid pharmaceutical preparation drug content measure analysis method, which is characterized in that using fixer as
The capillary column of -95% methyl polysiloxane of 5% phenyl is chromatographic column, is measured using gas-chromatography (GC) method.
2. the analysis method that drug content measures in amantadine hydrochloride solid pharmaceutical preparation according to claim 1, feature
It is, the chromatographic condition and system suitability of gas-chromatography (GC) method are as follows：
Chromatographic condition：Using the capillary column that fixer is -95% methyl polysiloxane of 5% phenyl as chromatographic column, initial temperature is
It 70 DEG C, maintains 5 minutes, is warming up to 250 DEG C with 10 DEG C per minute of rate, maintains 17 minutes, injector temperature is 220 DEG C, inspection
It is 300 DEG C to survey device temperature；
System suitability：Amantadine hydrochloride and each 5mg of adamantane reference substance are weighed respectively, are placed in 10ml measuring bottles, are added trichlorine
Methane dissolves, until scale, shakes up, both；It is required that amantadine hydrochloride peak and the separating degree at adamantane peak are more than 20, amantadine
The signal-to-noise ratio of peak height should be greater than 30.
3. the analysis method that drug content measures in amantadine hydrochloride solid pharmaceutical preparation according to claim 2, feature
It is, the assay method of gas-chromatography (GC) method is as follows：
(1) preparation of test solution：Precision weighs Symmetrel, is equivalent to amantadine hydrochloride 75mg, weighed,
Put in 50ml measuring bottles, chloroform is added to dissolve and be diluted to scale, shake up to get；
(2) preparation of reference substance solution：Take amantadine hydrochloride reference substance appropriate, it is accurately weighed, chloroform is added to be configured to often
The solution of 1ml saliferous symmetrels 1.5mg to get；
(3) it is accurate to measure test solution and each 2 μ l injections gas chromatograph of reference substance solution, chromatogram is recorded, calculates golden
Firm alkane content.
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Citations (6)
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| CN1528736A (en) * | 2003-10-10 | 2004-09-15 | 常州市东吴医药化工技术开发有限公司 | Method for preparing amantadine sulfate |
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| CN101797277A (en) * | 2010-04-01 | 2010-08-11 | 贵州百灵企业集团制药股份有限公司 | Method for detecting Jingan capsule |
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