CN103926359B - The assay method of residual solvent in a kind of bulk drug mifepristone - Google Patents
The assay method of residual solvent in a kind of bulk drug mifepristone Download PDFInfo
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Abstract
The invention discloses the assay method of residual solvent in a kind of bulk drug mifepristone, by setting up item gas chromatograph analytic approach, the chromatogram of the standard solution chromatogram of the tetrahydrofuran of mensuration, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene and bulk drug mifepristone need testing solution is compared, calculates, has carried out the detection method of residual solvent in bulk drug mifepristone.The operation of this assay method is simple fast, highly sensitive, reproducible, result is accurate, and quantitatively can detect tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and the benzene equal solvent that may remain in bulk drug mifepristone, good reference is provided for controlling organic solvent residual in bulk drug mifepristone production technology, ensure the quality of mifepristone bulk drug, thus improve the security of clinical application, for the quality standard improving mifepristone bulk drug provides method foundation.
Description
Technical field
The present invention relates to a kind of assay method of steroidal antiprogestin bulk drug residual solvent, be specifically related to the assay method of residual solvent in bulk drug mifepristone.
Background technology
Mifepristone is the kind that China's coastal port records, and is the medicine of a kind of Robust speaker feature developed in recent years, has termination of early pregnancy, anti-implantation, induction menstruation and promotes uterotonic effect.This medicine needs to use the organic solvents such as ethanol, tetrahydrofuran, isopropyl ether, ethyl acetate, acetonitrile, benzene, methylene chloride and pyridine in preparation technology, benzene belongs to a class flux, because methylene chloride, acetonitrile, tetrahydrofuran, pyridine belong to Equations of The Second Kind solvent, toxicity is larger, use should be limited, and ethanol, ethyl acetate belong to the 3rd kind solvent, use at drug's GMP or the restriction of other quality requirementss, therefore be necessary effectively to control their content in quality standard.
Tetrahydrofuran, alcohol, isopropyl ether, ethyl acetate, methylene chloride, acetonitrile, benzene all belong to organic solvent, to skin, respiratory mucosa, eye conjunctiva etc., there is certain spread effect, contact high concentration can cause toxic encephalopathy, has dizziness, headache, the disturbance of consciousness in various degree and even stupor.
Wherein, benzene is a kind of colourless, liquid with special aromatic odor, and can dissolve each other with alcohol, ether, acetone and phenixin, be slightly soluble in water, be IARC first kind carcinogenic substance, frequent Contact benzene, skin can because of degreasing desiccation, furfur, some appearance allergic eczemas; Long-term suction benzene can cause dirt aplastic anemia again.Tetrahydrofuran has stimulation and anesthetic action; Cause the upper respiratory tract to stimulate after suction, feel sick, dizzy, headache and central nervous system impression; Liver, renal damage can be caused; Liquid or high concentration steam irritant to eye.
Ethanol belongs to micro-virus kind, but anesthetic action is larger than methyl alcohol, and its main effects produces caused by suppression central nervous system.When ethanol intake increases, its central nervous system inhibiting effect strengthens, and first acts on cerebral cortex, then affects subcortical center, can cause oblongata vasomotor center and respiratory center paralysis.Isopropyl ether route of entry: suck, eat, percutaneous absorbtion; Its health hazard: steam or mist irritant to eyes, mucous membrane, skin and the upper respiratory tract; Can cause nausea after contact, have a headache, vomit and anesthetic action; Skin contact repeatedly, can cause contact dermatitis.
Ethyl acetate has spread effect to eye, nose, throat; High concentration sucks can cause slow and progressive anesthetic action; Continue a large amount of suction, can respiratory paralysis be caused; There is sensitization, cause the hyperemia of gum road and mucosal inflammation because of nervus vasculairs obstacle; Eczema-like dermatitis can be caused.Methylene chloride has anesthetic action, major determinant nervous centralis and respiratory system; Its toxicity: per os belongs to moderate toxicity; Its acute toxicity: open-assembly time increases, and has slight hepatatrophy, steatosis and cellular infiltration.
Pyridine health hazard: have intense stimulus; Central nervous system can be anaesthetized; Spread effect is had to eye and the upper respiratory tract; After high concentration sucks, the lighter has glad or sensation of asphyxia, then occurs depression, myasthenia, vomiting; The severe one loss of consciousness, gatism, tonic spasm, blood pressure drops; Wrongly taking can be lethal.Chronic Effect: eat for a long time and occur that dizziness, headache, insomnia, instability of gait and digestive tract function are disorderly; Hepatorenal damage can be there is.Dermatitis can be caused.
Acetonitrile acute poisoning comparatively hydrogen cyanide of falling ill is slow, can have latent period a few hours.Cardinal symptom be weak, unable, complexion is greyish white, Nausea and vomiting, stomachache, diarrhoea, uncomfortable in chest, pectoralgia; Severe patient is breathed and circulation system disorder, and breathe shallow, slow and irregular, blood pressure drops, pulse is thin and slowly, temperature decline, paroxysmal is twitched, stupor.Frequent micturition, albuminuria etc. can be had.
If do not carry out limit test to dissolvent residual in medicine, medicine will be made to there is great potential safety hazard.
Summary of the invention
The object of the present invention is to provide the assay method of residual solvent in a kind of bulk drug mifepristone, set up item gas chromatograph analytic approach to detect the organic solvent that may remain in bulk drug mifepristone, operation is simple fast, highly sensitive, reproducible, result is accurate, and can quantitatively detect the tetrahydrofuran that may remain in bulk drug mifepristone, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile, the organic solvents such as benzene, good reference is provided for controlling organic solvent residual in bulk drug mifepristone production technology, ensure the quality of mifepristone bulk drug, thus improve the security of clinical application, for the quality standard improving mifepristone bulk drug provides method foundation.
To achieve these goals, the present invention adopts following technical scheme:
An assay method for residual solvent in bulk drug mifepristone, comprises the following steps:
(1) control substance of plant drug is selected: select tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene material in contrast; The purity grade of above-mentioned control substance of plant drug is analyzes pure AR;
(2) need testing solution is prepared: accurately take mifepristone test sample, be placed in headspace sampling bottle, add dimethyl sulfoxide (DMSO), ultrasonic dissolution, shake up rear as need testing solution, in wherein said mifepristone need testing solution, the concentration of mifepristone is preferably 0.2g/ml;
(3) preparation standard product solution: accurately take reference substance ethanol respectively, tetrahydrofuran, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile be dissolved in and have in the volumetric flask of dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up to obtain the first mixed solution; Accurately take reference substance benzene and be placed in the volumetric flask with dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up to obtain the second solution;
A certain amount of first mixed solution and the second solution are placed in a volumetric flask, add dimethyl sulfoxide (DMSO) and be diluted to scale, after shaking up, obtain standard solution, this standard solution solution in contrast;
Wherein, in described standard solution, the concentration of each reference substance is preferably: ethanol 200 μ g/mL; Tetrahydrofuran 144 μ g/mL; Isopropyl ether 200 μ g/mL; Ethyl acetate 400 μ g/mL; Methylene chloride 120 μ g/mL, pyridine 40 μ g/mL, acetonitrile 82 μ g/mL, benzene 0.4 μ g/mL;
(4) headspace gas chromatography sample introduction standard solution spininess and need testing solution spininess is respectively adopted, obtain the chromatogram of standard solution and the chromatogram of need testing solution respectively, by the peak area of each residual solvent respective peaks in the peak area of reference substance respective peaks each in standard solution chromatogram and need testing solution chromatogram, following formulae discovery is adopted to obtain the content of each residual solvent in bulk drug mifepristone, i.e. the content of tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene in mifepristone:
In formula: the peak area of each residual solvent in As-need testing solution;
The dilution volume of V-mifepristone test sample, Unit/mL; The i.e. dilution volume of step (2);
The concentration of corresponding residual solvent in C-standard solution, unit mg/mL;
W
sample-sample weighing, unit mg;
the average peak area of corresponding residual solvent in-standard solution.
Wherein, headspace gas chromatography is adopted to carry out measuring relative standard deviation RSD≤10% requiring each solvent peak peak area; Degree of separation >=1.5 between adjacent solvent.
Preferably, before sample introduction standard solution spininess and need testing solution spininess first sample introduction blank solution 1 pin as blank; Sample introduction standard solution spininess is 6 pins, and sample introduction need testing solution spininess is 2 pins.
Preferably, when adopting the content of each residual solvent in Headspace Gas Chromatography bulk drug mifepristone, its condition determination is:
Adopt AgilentDB-624 fused-silica capillary column (30m × 0.53mm × 3 μm) as analysis chromatographic column, detecting device is fid detector;
Chromatographic resolution parameter: carrier gas: nitrogen; Flow rate of carrier gas: 3.0mL/min; Split ratio: 10:1;
Detector temperature: 250 DEG C; Injector temperature: 200 DEG C;
Column temperature: initial temperature is 45 DEG C, keeps 10min, with the heating rate to 150 DEG C of 15 DEG C/min, keeps 3min;
Head space detected parameters: heating cabinet: 105 DEG C; Quantitative loop: 115 DEG C; Transmission line: 125 DEG C;
Gas phase GC cycling time: 25min; Sample injection time: 1min;
Sample equilibration time: 20min; Pressure balance time: 0.2min.
The present invention is many because bulk drug mifepristone sample relates to residual solvent kind, boiling point is wider, for adapting to the detection of residual solvent in bulk drug mifepristone, need the testing conditions that selection and comparison is suitable, adopted initial column temperature, heating rate are adjusted, through the optimization to other each controlled conditions above-mentioned, finally determine column temperature initial temperature 45 DEG C, keep 10min, with the heating rate to 150 DEG C of 15 DEG C/min, keep 3min.Head space detected parameters: heating cabinet: 105 DEG C of quantitative loop: 115 DEG C, transmission line: 125 DEG C, GC cycling time: 25min, sample injection time: 1min, Sample equilibration time: 20min, pressure balance time: 0.2min.
The assay method of residual solvent in bulk drug mifepristone of the present invention, RSD≤10% of each solvent peak area in its system flexibility contrast liquid; Degree of separation >=1.5 between adjacent solvent; Specificity is following 3 points: 1. blank does not have other impurity peaks, if had, must not disturb detected solvent; 2. the solvent of all checkings is answered separated from one another and is separated with related solvent, degree of separation >=1.5; 3. the residual solvent of all the unknowns should be separated with all residual solvents be verified.RSD≤10% of its precision, repeated each solvent peak area.
The assay method of residual solvent in bulk drug mifepristone of the present invention, by setting up head space gas chromatography method, the chromatogram of the standard solution chromatogram of the tetrahydrofuran of mensuration, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene and bulk drug mifepristone need testing solution is compared, calculates, has carried out the detection method of residual solvent in bulk drug mifepristone.The operation of this assay method is simple fast, highly sensitive, reproducible, result is accurate, and quantitatively can detect tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and the benzene equal solvent that may remain in bulk drug mifepristone, good reference is provided for controlling organic solvent residual in bulk drug mifepristone production technology, ensure the quality of mifepristone bulk drug, thus improve the security of clinical application, for the quality standard improving mifepristone bulk drug provides method foundation.
Accompanying drawing explanation
Fig. 1-1 is blank solution chromatogram.
Fig. 1-2 is the headspace gas chromatography figure of the 1st pin standard solution.
Fig. 1-3 is item gas chromatograph figure of the 2nd pin standard solution.
Fig. 1-4 is headspace gas chromatography figure of the 3rd pin standard solution.
Fig. 1-5 is headspace gas chromatography figure of the 4th pin standard solution.
Fig. 1-6 is headspace gas chromatography figure of the 5th pin standard solution.
Fig. 1-7 is headspace gas chromatography figure of the 6th pin standard solution.
Fig. 2-1 is the headspace gas chromatography figure of 1# bulk drug mifepristone need testing solution the 1st pin.
Fig. 2-2 is item gas chromatograph figure of 1# bulk drug mifepristone need testing solution the 2nd pin.
Fig. 2-3 be 2# bulk drug mifepristone need testing solution the 1st pin headspace gas chromatography figure.
Fig. 2-4 be 2# bulk drug mifepristone need testing solution the 2nd pin headspace gas chromatography figure.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described.Should be understood that following examples only for illustration of the present invention but not for limiting protection scope of the present invention.
The mensuration of residual solvent in embodiment 1 bulk drug mifepristone
(1) analytical approach: head space gas chromatography method.
Chromatographic system:
Chromatographic column: AgilentDB-624 fused-silica capillary column (30m × 0.53mm × 3 μm), fid detector.
Chromatographic parameter:
Chromatographic resolution parameter: carrier gas: nitrogen; Flow rate of carrier gas: 3.0mL/min; Split ratio: 10:1;
Detector temperature: 250 DEG C; Injector temperature: 200 DEG C;
Column temperature: initial temperature 45 DEG C, keeps 10min, with the heating rate to 150 DEG C of 15 DEG C/min, keeps 3min.
Head space detected parameters: heating cabinet: 105 DEG C; Quantitative loop: 115 DEG C; Transmission line: 125 DEG C;
GC cycling time: 25min; Sample injection time: 1min;
Sample equilibration time: 20min; Pressure balance time: 0.2min.
(2) solution preparation:
1, reference substance solution (i.e. standard solution):
Accurately take ethanol 200mg, tetrahydrofuran 144mg, isopropyl ether 200mg, ethyl acetate 400mg, methylene chloride 120mg, pyridine 40mg, acetonitrile 82mg is dissolved in has in the 100mL volumetric flask of appropriate dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up solution 1..
Accurately take the 100mL volumetric flask that benzene 40mg is placed in appropriate dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up.Accurately measure this solution 1.0mL in 100mL volumetric flask, add dimethyl sulfoxide (DMSO) and be diluted to scale, shake up solution 2..
Pipette solution 1. with solution 2. each 10.0mL in 100mL volumetric flask, add dimethyl sulfoxide (DMSO) and be diluted to scale, shake up, product solution in contrast.Pipette reference substance solution 5.0mL be placed in 20mL ml headspace bottle and get final product.Wherein in reference substance solution, the concentration of each reference substance is: ethanol 200 μ g/mL; Tetrahydrofuran 144 μ g/mL; Isopropyl ether 200 μ g/mL; Ethyl acetate 400 μ g/mL; Methylene chloride 120 μ g/mL, pyridine 40 μ g/mL, acetonitrile 82 μ g/mL, benzene 0.4 μ g/mL.
2, need testing solution:
Accurately take 1.000g test sample, be placed in the empty sample injection bottle of 20mL item, add 5.0mL dimethyl sulfoxide (DMSO), ultrasonic dissolution, shake up, as need testing solution.
(3) determination step:
Sample introduction blank solution 1 pin, its chromatogram is as Figure 1-1;
Sample introduction reference substance solution 6 pin, obtains chromatogram, records the peak area (as shown in table 2) of each reference substance respective peaks, require that the RSD of each reference substance peak area must not be greater than 10%;
Sample introduction need testing solution 2 pin, record chromatic graph spectrum, by the peak area of each residual solvent respective peaks in the peak area of reference substance respective peaks each in reference substance solution chromatogram and need testing solution chromatogram, following formulae discovery is adopted to obtain the content of each residual solvent in bulk drug mifepristone, i.e. the content of tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene in mifepristone:
According to each residual solvent levels of calculated by peak area, computing formula is as follows:
In formula: the peak area of each residual solvent in As-sample solution;
V-mifepristone Sample Dilution volume, Unit/mL;
The concentration of corresponding residual solvent in C-standard solution, unit mg/mL;
W
sample-sample weighing, unit mg;
the average peak area of corresponding residual solvent in-standard solution.
(4) detection and result:
In contrast solution, the system flexibility weighing value of each reference substance component is as shown in table 1.
Table 1 system flexibility weighing value
Detect sample introduction reference substance solution 6 pin by above-mentioned steps, obtain chromatogram (as shown in 1-2 to Fig. 1-7) and record each peak-to-peak area, require that RSD must not be greater than 10%, its result is as shown in table 2:
Table 2 system flexibility test result
Note: R'min is the degree of separation between the most difficult separation component (acetonitrile and methylene chloride).
Get 2 batches of bulk drug mifepristone samples (as shown in table 3) respectively, by above-mentioned determine after chromatographic condition carry out By Headspace Gas Chromatography, record testing result, as shown in table 2 identical of system flexibility result wherein.
Table 3
| Bulk drug lot number | 30011204001 | 3001120402 |
| 1# | 1.0095g | 0.9993g |
| 2# | 1.0102g | 1.0012g |
Sample introduction need testing solution 2 pin, record chromatic graph spectrum, when being measured by headspace gas chromatography instrument by need testing solution, its chromatographic condition is identical with the chromatographic condition of standard solution, obtains test sample chromatogram, and its chromatogram is as shown in Fig. 2-1 and Fig. 2-2.
The concrete outcome obtained by the content formulae discovery of each residual solvent in above-mentioned raw materials medicine mifepristone is as shown in table 4.Relatively the chromatogram of need testing solution and standard solution is known, ethanol and acetonitrile peak area are less than standard solution ethanol and acetonitrile peak area, then ethanol and acetonitrile component limit meet statutory standards, and other solvents tetrahydrofurane, isopropyl ether, ethyl acetate, methylene chloride, pyridine, benzene do not detect.
Table 4
(5) Method validation is carried out to the detection method of each residual solvent in above-mentioned raw materials medicine mifepristone: comprise each solvent peak peak area RSD≤10% (RSD as shown in table 2 is 5.57% to the maximum) in system flexibility contrast liquid; Degree of separation >=1.5 (degree of separation >=2.66 between the most difficult separation component acetonitrile as shown in table 2 and methylene chloride) between adjacent solvent.
Specificity: 1. blank does not have other impurity peaks, if had, must not disturb detected solvent; 2. the solvent of all checkings is answered separated from one another and is separated with related solvent, degree of separation >=1.5; 3. the residual solvent of all the unknowns should be separated with all residual solvents be verified.
Precision, repeated each solvent peak area RSD≤10%, fiducial interval (95%).
As shown in Table 5, its accuracy, average recovery rate are 80% ~ 120%.
Table 5 accuracy test result
Note: the A in above-mentioned table 5
0for the average peak area of solvent each in need testing solution, A
ufor the peak area of solvent each in accuracy solution.
As shown in Table 5, the recovery of each solvent all meets the requirements, and shows that this detection method accuracy is good.
Detectability and quantitative limit: the low concentration solution that a signal to noise ratio (S/N ratio) >=10 prepared by all solvents that need verify is measured.By following formula by calculating quantitative limit QL.Detectability is drawn by the relation of quantitative limit.
QL＝10C/(S/N)
Wherein: S/N: the signal to noise ratio (S/N ratio) of the low concentration solution of >=10,
C: the concentration representing above-mentioned low concentration solution.
Detectability (DL): inferred by quantitative limit QL and calculate:
(1) concrete process for preparation is as follows: be configured according to the method for the reference substance solution (i.e. standard solution) under solution preparation item in embodiment 1, and wherein in the weighing value of reference substance and reference substance solution, the concentration of each reference substance is as shown in table 6.
(2) sample introduction operation steps: each reference substance solution repeats sample introduction 3 times, the corresponding chromatogram of follow procedure record.
(3) test result is as shown in table 6.
The each solvent quantitative limit of table 6 and detectability test result
Note: * represents the ppm concentration relative to reference substance.
Its testing result: as shown in Table 6, in mixing reference substance solution, QL and DL of each solvent is much smaller than limit value.
Linear correlation degree is investigated:
Investigate l.o.i quantitative limit to limit 120% between linear case, linearly dependent coefficient R
2answer>=0.99.
Get respectively at 6 and do linear investigation, according to above-mentioned aqueous standard method product solution and dilute concentration is 20%, 40%, 60%, 80%, 100%, 120% μ g/mL.
Get the linear solvent 5mi of each concentration respectively, adopt headspace gas chromatography headspace sampling, each replication 3 times, follow procedure record chromatogram, obtain equation of linear regression result as follows:
Ethanol: y=0.5735 ×-0.2467R
2=0.9992;
Acetonitrile: y=0.4536 ×-1.4736R
2=0.9967;
Methylene chloride: y=0.5639 ×+0.0231R
2=0.9993;
Isopropyl ether: y=0.0225 ×+1.0181R
2=0.9990;
Ethyl acetate: y=0.1647 ×+0.1476R
2=0.9994;
Benzene: y=0.798 ×-0.1028R
2=0.9949;
Tetrahydrofuran: y=0.0966 ×-0.0339R
2=0.9995;
Pyridine: y=1.3109 ×-0.7997R
2=0.9960.
Each linearly dependent coefficient R in above-mentioned linear correlation degree
2>=0.99, meet the requirements.
Durability, initial column temperature ± 5 DEG C, flow rate of carrier gas+0.2mL/min, stability of solution meets system flexibility requirement; Each solvent peak area RSD≤10%.
In bulk drug mifepristone of the present invention residual solvent assay method in, in bulk drug mifepristone, residual solvent is by above-mentioned experimental verification, its result is all accepting, between standard, to meet the requirements, and therefore this assay method can detect residual solvent detection in bulk drug mifepristone.
Above-described embodiment is illustrative principle of the present invention and effect thereof only, but not for limiting the present invention.Any person skilled in the art scholar all without prejudice under spirit of the present invention and category, can modify above-described embodiment or changes.Therefore, such as have in art usually know the knowledgeable do not depart from complete under disclosed spirit and technological thought all equivalence modify or change, must be contained by claim of the present invention.
Claims (5)
1. the assay method of residual solvent in bulk drug mifepristone, comprises the steps:
(1) control substance of plant drug is selected: select tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene material in contrast;
(2) prepare need testing solution: accurately take mifepristone test sample, be placed in headspace sampling bottle, add dimethyl sulfoxide (DMSO), ultrasonic dissolution, shake up rear as need testing solution;
(3) preparation standard product solution: accurately take reference substance tetrahydrofuran respectively, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile be dissolved in and have in the volumetric flask of dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up to obtain the first mixed solution; Accurately take reference substance benzene and be placed in the volumetric flask with dimethyl sulfoxide (DMSO), and be diluted to scale with dimethyl sulfoxide (DMSO), shake up to obtain the second solution;
A certain amount of first mixed solution and the second solution are placed in a volumetric flask, add dimethyl sulfoxide (DMSO) and be diluted to scale, after shaking up, obtain standard solution, this standard solution solution in contrast;
(4) headspace gas chromatography sample introduction standard solution spininess and need testing solution spininess is respectively adopted, obtain the chromatogram of standard solution and the chromatogram of need testing solution respectively, by the peak area of each residual solvent respective peaks in the peak area of reference substance respective peaks each in standard solution chromatogram and need testing solution chromatogram, following formulae discovery is adopted to obtain the content of each residual solvent in bulk drug mifepristone, i.e. the content of tetrahydrofuran, ethanol, isopropyl ether, ethyl acetate, methylene chloride, pyridine, acetonitrile and benzene in mifepristone:
In formula: the peak area of each residual solvent in As-need testing solution;
The dilution volume of V-mifepristone test sample, Unit/mL;
The concentration of corresponding residual solvent in C-standard solution, unit mg/mL;
W
sample-sample weighing, unit mg;
the average peak area of corresponding residual solvent in-standard solution;
Wherein, when adopting the content of each residual solvent in Headspace Gas Chromatography bulk drug mifepristone, its condition determination is:
Adopt AgilentDB-624 fused-silica capillary column as analysis chromatographic column, detecting device is fid detector;
Chromatographic resolution parameter: carrier gas: nitrogen; Flow rate of carrier gas: 3.0mL/min; Split ratio: 10:1;
Detector temperature: 250 DEG C; Injector temperature: 200 DEG C;
Column temperature: initial temperature is 45 DEG C, keeps 10min, with the heating rate to 150 DEG C of 15 DEG C/min, keeps 3min;
Head space detected parameters: heating cabinet: 105 DEG C; Quantitative loop: 115 DEG C; Transmission line: 125 DEG C;
GC cycling time: 25min; Sample injection time: 1min;
Sample equilibration time: 20min; Pressure balance time: 0.2min.
2. the assay method of residual solvent in bulk drug mifepristone as claimed in claim 1, it is characterized in that, in step (2), in described mifepristone need testing solution, the concentration of mifepristone is 0.2g/ml.
3. the assay method of residual solvent in bulk drug mifepristone as claimed in claim 1, it is characterized in that, in step (3), in described standard solution, the concentration of each reference substance is: ethanol 200 μ g/mL; Tetrahydrofuran 144 μ g/mL; Isopropyl ether 200 μ g/mL; Ethyl acetate 400 μ g/mL; Methylene chloride 120 μ g/mL, pyridine 40 μ g/mL, acetonitrile 82 μ g/mL, benzene 0.4 μ g/mL.
4. the assay method of residual solvent in bulk drug mifepristone as claimed in claim 1, is characterized in that, adopt headspace gas chromatography to carry out measuring relative standard deviation RSD≤10% requiring each solvent peak peak area; Degree of separation >=1.5 between adjacent solvent.
5. the assay method of residual solvent in bulk drug mifepristone as claimed in claim 1, is characterized in that, before sample introduction standard solution spininess and need testing solution spininess, first sample introduction blank solution 1 pin is as blank; Sample introduction standard solution spininess is 6 pins, and sample introduction need testing solution spininess is 2 pins.
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