CN105823845A - Capecitabine determination and application thereof - Google Patents
Capecitabine determination and application thereof Download PDFInfo
- Publication number
- CN105823845A CN105823845A CN201610308274.6A CN201610308274A CN105823845A CN 105823845 A CN105823845 A CN 105823845A CN 201610308274 A CN201610308274 A CN 201610308274A CN 105823845 A CN105823845 A CN 105823845A
- Authority
- CN
- China
- Prior art keywords
- amyl alcohol
- capecitabine
- sample
- temperature
- solution
- 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.)
- Granted
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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/16—Injection
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/025—Gas chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/884—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample organic compounds
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention discloses capecitabine determination and application thereof. A direct injection method is selected, an organic solvent with the boiling point lower than 70 DEG C under the normal pressure is adopted as a solvent, the temperature of an injection port is 60-75 DEG C, degradation of capecitabine is effectively controlled, and the problem that a capecitabine sample disturbs determination of the content of n-amyl alcohol due to high-temperature degradation is solved. The verification test reproducibility is good, the linear relation is good, the average recovery rate is good, and n-amyl alcohol possibly remaining in the capecitabine sample can be accurately and quantitatively detected out. The content of n-amyl alcohol in the sample is accurately determined, and meanwhile the quality of capecitabine and safety of drug use are ensured.
Description
Technical field
The invention belongs to medicine analysis technical field, be specifically related to mensuration and the application thereof of a kind of capecitabine.
Background technology
Capecitabine, English entitled Capecitabine, it it is a kind of antimetabolic fluoropyrimidine deoxynucleoside carbamates medicine that can be transformed into 5-FU in vivo, developed by Roche Holding Ag, trade name xeloda, it is possible to suppression cell division and RNA interfering and protein (protein) synthesis.It is applicable to paclitaxel and includes advanced primary or the further treatment of metastatic breast cancer that anthracycline antibiotics chemotherapy regimen is failed to respond to any medical treatment.It is mainly used in advanced primary or metastatic breast cancer, the treatment of rectal cancer, colon cancer and gastric cancer.Its structural formula is as follows:
Chinese invention patent CN201080032544.6, CN201010134093.9 and CN201110090029.X, when preparing capecitabine, use n-amyl alcohol；It addition, through the structural analysis to capecitabine, n-amyl alcohol may be degraded in synthesis or placement process, therefore the residual quantity of n-amyl alcohol in finished product is studied.During capecitabine residual solvent measures headspace sampling, sample chromatogram figure has the biggest n-amyl alcohol peak, speculating under the conditions of temperature of vaporization chamber 200 DEG C, capecitabine sample has been degraded generation n-amyl alcohol, have impact on the mensuration of n-amyl alcohol content in capecitabine sample.
When the residual of residual solvent is higher than safety value, if dissolvent residual in medicine not being carried out limit test, it will make medicine there is greatly potential safety hazard.
Not yet have been reported that the assay of n-amyl alcohol in capecitabine at present, therefore, according to the guideline requirement of drug evaluation center, need to set up the content assaying method of n-amyl alcohol in a kind of capecitabine, and specify reasonably to limit, the safe medication guaranteeing capecitabine is had great importance.
Summary of the invention
It is an object of the invention to provide mensuration and the application thereof of a kind of capecitabine.Solve capecitabine sample because of the high temperature degradation interference problem to n-amyl alcohol assay.
In order to solve above-mentioned technical problem, the present invention is addressed by following technical proposals:
In a kind of capecitabine, the assay method of residual solvent, comprises the steps:
Prepared by A, need testing solution: take capecitabine sample, dissolves and be diluted to the solution of 0.01g/ml with the organic solvent less than 70 DEG C of the boiling point under normal pressure, and mixing is standby；
Prepared by B, reference substance solution: his middle Binhai residual solvent sample is trained in card taking, makes the solution of 500 μ g/ml with the organic solvent diluting less than 70 DEG C of the boiling point under normal pressure, mixes, standby；
C, detection method: take need testing solution and each 1 μ l of reference substance solution, be injected separately in the gas chromatographic column of gas chromatograph, record chromatogram successively；
D, cubage: by external standard method with the content of calculated by peak area residual solvent.
As preferably, described residual solvent is n-amyl alcohol.
As preferably, under described normal pressure, the boiling point organic solvent less than 70 DEG C is any one in t-butyl methyl ether, acetone, normal hexane and dichloromethane, more preferably dichloromethane.
The present invention selects under normal pressure boiling point low organic solvent as solvent, thus reduces the vapourizing temperature of injection port vaporizer, avoids the high-temperature evaporation degraded to sample to greatest extent, thus affects the accuracy of measurement result.
As preferably, detection method described in step C is direct injected gas chromatography.
The present invention uses direct-injection technique, simple to operate, requires low to gas phase relevant device, has evaded headspace sampling mode crude drug and the big shortcoming of solvent-oil ratio.Avoid head space algoscopy high-temperature heating long to sample head space to cause the degraded of sample simultaneously, thus affect the accuracy of measurement result.
As preferably, the chromatographic column model of described gas chromatograph is: 6% cyanogen propyl group phenyl-94% dimethyl polysiloxane is the capillary column of fixative, the column length 30m of this quartz capillary column, internal diameter 0.32mm, thickness of liquid film 3 μm.
As preferably, the gas chromatogram column condition of direct-injection technique is:
Column temperature: temperature programming；
Injector temperature: 60～75 DEG C；
Flame ionization detector temperature: 180～250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.2～3.2ml/min；
Split ratio: 5:1～15:1.
Further, gas chromatogram column condition is:
Column temperature: temperature programming method is that initial temperature 60 DEG C keeps 2 minutes, then with the ramp of 15 DEG C per minute to 200 DEG C, keeps 5 minutes；
Injector temperature: 70 DEG C；
Flame ionization detector temperature: 250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.7ml/min；
Split ratio: 10:1.
Another object of the present invention there is provided the application using first arbitrary assay method of purpose of the present invention in detection capecitabine finished product in n-amyl alcohol content.
The 3rd purpose of the present invention there is provided the checking linear test using first arbitrary assay method of purpose of the present invention, comprises the steps:
1) taking n-amyl alcohol appropriate, accurately weighed, the dichloromethane solution containing n-amyl alcohol 0.5mg/ml is made in dilution；
2) precision pipettes 0.2ml, 0.5ml, 1ml, 1.2ml, 1.5ml in 10ml volumetric flask respectively, uses dchloromethane constant volume, shakes up, standby；
3) precision measures step 2 respectively) in each 2 μ l sample introductions of sample, direct injected, record chromatogram；
4) with concentration as x-axis, peak area is y-axis, makees linear regression.
The present invention uses above-mentioned checking linear test, and linear relationship is good.
The 4th purpose of the present invention there is provided the checking recovery test using first arbitrary assay method of purpose of the present invention, comprises the steps:
1) taking n-amyl alcohol appropriate, accurately weighed, dilution makes the dichloromethane solution containing n-amyl alcohol 0.5mg/ml as stock solution；
2) this product about 0.1g is taken, accurately weighed, put in 10ml volumetric flask, add q. s. methylene chloride and make dissolving, precision measures 0.8ml respectively, and 1ml, 1.2ml contrast solution is in 10ml volumetric flask, and add methylene chloride dilution constant volume.Direct injected, records chromatogram；
3) another precision measures 1ml stock solution in the volumetric flask of 10ml, adds methylene chloride and is diluted to scale, shake up, be measured in the same method, calculates its response rate.
The present invention uses above-mentioned checking recovery test, result show test the response rate all between 80%～120%, result meets the requirements, and the method response rate is good.
Compared with prior art, the Advantageous Effects that the present invention brings is as follows:
The present invention provides a kind of simple to operate, detection method that precision is high, and the method precision relative standard deviation is only 3.1%, and repeatability is more preferable, and precision test checking is good；Degraded to capecitabine sample simultaneously has carried out effective control, has carried out measuring accurately to the content of n-amyl alcohol in sample, it is achieved that effective quality control, thus ensure that the quality of capecitabine.
Accompanying drawing explanation
Fig. 1 is the detection spectrogram of the n-amyl alcohol in embodiment 1 in capecitabine.
Fig. 2 is n-amyl alcohol reference substance solution chromatogram in embodiment 1.
Fig. 3 is embodiment 1 empty solvent chromatogram.
Fig. 4 is n-amyl alcohol detection limit chromatogram in embodiment 1.
Fig. 5 is the linear relationship chart of n-amyl alcohol in embodiment 1.
Detailed description of the invention
1, instrument:
Analytical balance, model: METTLERTOLEDOABS135-S.
Gas chromatograph model is Agilent7890A, chromatographic column model is HP-INNOWAX: the quartz capillary column with Polyethylene Glycol as fixative, the column length 30m of this quartz capillary column, internal diameter 0.32mm, thickness of liquid film 3 μm.
2, capecitabine sample: lot number: KP0901, KP0902, KP0903.
Below in conjunction with embodiment, the present invention is further elaborated, but these embodiments do not constitute any restriction to the present invention.
Embodiment 1
The chromatographic condition of direct-injection technique:
Column temperature: temperature programming: initial temperature 60 DEG C keeps 2 minutes, then with the ramp of 15 DEG C per minute to 200 DEG C, keeps 5 minutes.
Injector temperature: 70 DEG C；
Flame ionization detector temperature: 250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.7ml/min；
Split ratio: 10:1.
1, detection
Prepared by A, need testing solution: take capecitabine sample, dissolves and be diluted to the solution of 0.01g/ml with dichloromethane, mixing, standby；
Prepared by B, reference substance solution: his middle Binhai residual solvent sample is trained in card taking, makes the solution of 500 μ g/ml with dichloromethane solution dilution, mixes, standby；
C, detection method: take need testing solution and each 1 μ l of reference substance solution, be injected separately in the gas chromatographic column of gas chromatograph, record chromatogram successively；See Fig. 1 and Fig. 2.
D, cubage: by external standard method with the content of calculated by peak area residual solvent.
2, computing formula:
Solvent residual amount (%)=(Ai × V/W)/(As/Cs) × 100%；
Wherein Ai: solvent peak area to be measured in need testing solution；
As: n-amyl alcohol reference substance solution main peak area；
Cs: n-amyl alcohol reference substance solution concentration (mg/ml)；
The sampling amount (mg) of sample during the preparation of W: need testing solution；
V: need testing solution dose volume (ml)；
3, measurement result
According to said determination method, three batches of test samples are detected, the results are shown in Table 1.
1: three batch of test sample testing result of table
| Lot number | KP0901 | KP0902 | KP0903 |
| N-amyl alcohol content (%) | 0.025 | 0.016 | 0.023 |
3, Method validation
3.1 blank assay
Precision measures in dichloromethane 5ml top set sky sample injection bottle, and sample introduction under above-mentioned chromatographic condition shows with the trace analysis of reference substance, the mensuration of solvent not disturbed specimen, dichloromethane solvent appearance time is shown in Fig. 3.
3.2 precision test
Precision weighs 6 parts of capecitabine sample, every part of 0.1g, puts respectively in 10ml volumetric flask, adds methylene chloride and be diluted to scale, shakes up, and measures, the results are shown in Table 2.
Table 2: Precision test result
Conclusion: relative standard deviation RSD of 6 parts of sample n-amyl alcohol content is 3.1%, and result shows, the method sample precision is good.
3.3 detection limit
Method: precision weighs n-amyl alcohol 50mg, becomes the solution of 7 variable concentrations, is shown in Table 3 with dchloromethane.
Testing by above-mentioned chromatographic condition, precision measures solution 1 μ l under each concentration, is injected separately into the gas chromatographic column of gas chromatograph, records chromatogram.
Table 3:
| Numbering | Concentration (μ g/ml) |
| 1# | 502.4 |
| 2# | 50.24 |
| 3# | 25.12 |
| 4# | 5.024 |
| 5# | 2.512 |
| 6# | 1.005 |
| 7# | 0.5024 |
Experimental result:
Measuring by reducing concentration method step by step, calculate according to S/N=3, the detection recording n-amyl alcohol is limited to 0.5024 μ g/ml, the amount of 0.005% in suitable sample；Fig. 4 is shown in by detection limit collection of illustrative plates.
3.4 linear test
Taking n-amyl alcohol appropriate, accurately weighed, the dichloromethane solution containing n-amyl alcohol 0.5mg/ml is made in dilution.
Precision pipettes 0.2ml, 0.5ml, 1ml, 1.2ml, 1.5ml in 10ml volumetric flask respectively, uses dchloromethane constant volume, shakes up.Direct injected, records chromatogram.
And with concentration as x-axis, peak area is y-axis, makees linear regression, the results are shown in Table 4.
Table 4: n-amyl alcohol range of linearity measurement result
| Numbering | Concentration (μ g/ml) | Peak area |
| 1# | 10.05 | 11.79 |
| 2# | 25.12 | 30.26 |
| 3# | 50.24 | 60.10 |
| 4# | 60.29 | 74.58 |
| 5# | 75.36 | 92.69 |
Concentration with peak area regression equation is:
Y=1.2401x-0.9425R2=0.9995
As a result, n-amyl alcohol is good in 10.05～75.36 μ g/ml concentration range internal linear.Linear relationship curve chart is shown in Fig. 6.
3.5 recovery test
Taking n-amyl alcohol appropriate, accurately weighed, dilution makes the dichloromethane solution containing n-amyl alcohol 0.5mg/ml as stock solution.Take this product 0.1g, accurately weighed, put in 10ml volumetric flask, add q. s. methylene chloride and make dissolving, precision measures 0.8ml respectively, and 1ml, 1.2ml contrast solution is in 10ml measuring bottle, and add methylene chloride dilution constant volume.Direct injected, records chromatogram.Another precision measures 1ml stock solution in the volumetric flask of 10ml, adds methylene chloride and is diluted to scale, shake up, be measured in the same method, calculates its response rate, the results are shown in Table 5.
Table 5: the n-amyl alcohol response rate
Result show test the response rate all between 80%～120%, result meets the requirements, and the method response rate is good.
Embodiment 2
In the same manner as in Example 1, the solvent adjusting need testing solution and reference substance solution is acetone；
Injector temperature: 60 DEG C；
Flame ionization detector temperature: 180 DEG C；
Flow rate of carrier gas: 2.2ml/min；
Split ratio: 5:1.
According to said determination method, three batches of test samples are detected, the results are shown in Table 6.
6: three batches of test sample testing results of table
| Lot number | KP0901 | KP0902 | KP0903 |
| N-amyl alcohol content (%) | 0.031 | 0.025 | 0.029 |
Embodiment 3
In the same manner as in Example 1, the solvent adjusting need testing solution and reference substance solution is normal hexane；
Injector temperature: 75 DEG C；
Flame ionization detector temperature: 250 DEG C；
Flow rate of carrier gas: 3.2ml/min；
Split ratio: 15:1.
According to said determination method, three batches of test samples are detected, the results are shown in Table 7.
7: three batches of test sample testing results of table
| Lot number | KP0901 | KP0902 | KP0903 |
| N-amyl alcohol content (%) | 0.017 | 0.009 | 0.018 |
Embodiment 4
In the same manner as in Example 1, the solvent adjusting need testing solution and reference substance solution is t-butyl methyl ether；
Injector temperature: 70 DEG C；
Flame ionization detector temperature: 250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.7ml/min；
Split ratio: 10:1.
According to said determination method, three batches of test samples are detected, the results are shown in Table 8.
8: three batches of test sample testing results of table
| Lot number | KP0901 | KP0902 | KP0903 |
| N-amyl alcohol content (%) | 0.022 | 0.017 | 0.021 |
Comparative example 5
In the same manner as in Example 1, only changing injector temperature, in detection KP0901 sample, n-amyl alcohol content results is shown in Table 9:
Table 9: different injector temperatures are on the impact of n-amyl alcohol content in sample
| Injector temperature: (DEG C) | 55 | 70 | 80 | 100 |
| N-amyl alcohol content (%) | 0.021 | 0.029 | 0.066 | 0.65 |
Result shows, when injector temperature is 55 DEG C, the most on the low side when the content of n-amyl alcohol is than 70 DEG C, but sample is more easy to quick and complete vaporization at 70 DEG C；When injector temperature is 80 DEG C, the content of n-amyl alcohol than 70 DEG C time higher, illustrate under conditions of 80 DEG C, during detection, to have Partial digestion be n-amyl alcohol to capecitabine；When injector temperature is 100 DEG C the content of n-amyl alcohol than 70 DEG C time the most higher, it is impossible to the accurately content of n-amyl alcohol in detection sample；Therefore injector temperature can detect the content of n-amyl alcohol in sample fast and accurately at 60～75 DEG C.
Comparative example 6
With reference to the experiment condition of the embodiment of the present invention 1, only changing solvent, in capecitabine sample, n-amyl alcohol content results is as follows:
Solvent 1 is methanol, boiling point 65 DEG C under normal pressure, and capecitabine sample exists methanol and n-amyl alcohol in this solvent and exchanges, and affects accuracy of measurement, and methanol to be difficult to fast vaporizing at 70 DEG C complete.
Solvent 2 is ethanol, boiling point 78 DEG C under normal pressure, and capecitabine sample exists ethanol in this solvent and exchanges with n-amyl alcohol, affects accuracy of measurement, and ethanol can not vaporize at 70 DEG C.
Solvent 3: because solvent boiling point is higher, such as acetonitrile (boiling point 81 DEG C under normal pressure), ethyl acetate (boiling point 77 DEG C under normal pressure), dimethyl sulfoxide, N, dinethylformamide, and the temperature of vaporization chamber that this experiment uses is 70 DEG C, cannot be used for direct injected detection, it is impossible to accurately n-amyl alcohol content in detection capecitabine sample.
Conclusion: although above-mentioned solvent polarity is close, but because of the particularity of capecitabine sample structure, the solvent using boiling point relatively low can accurately detect the content of n-amyl alcohol in capecitabine sample.
The explanation of above example is only intended to help to understand method and the core concept thereof of the present invention.It should be pointed out that, for the person of ordinary skill of the art, under the premise without departing from the principles of the invention, it is also possible to the present invention is carried out some improvement and modification, these improve and modify in the protection domain also falling into the claims in the present invention.
Claims (10)
1. an assay method for residual solvent in capecitabine, comprises the steps:
Prepared by A, need testing solution: take capecitabine sample, dissolves and be diluted to the solution of 0.01g/ml with the organic solvent less than 70 DEG C of the boiling point under normal pressure, and mixing is standby；
Prepared by B, reference substance solution: his middle Binhai residual solvent sample is trained in card taking, makes the solution of 500 μ g/ml with the organic solvent diluting less than 70 DEG C of the boiling point under normal pressure, mixes, standby；
C, detection method: take need testing solution and each 1 μ l of reference substance solution, be injected separately in the gas chromatographic column of gas chromatograph, record chromatogram successively；
D, cubage: by external standard method with the content of calculated by peak area residual solvent.
Assay method the most according to claim 1, it is characterised in that described residual solvent is n-amyl alcohol.
Assay method the most according to claim 1 and 2, it is characterised in that under described normal pressure, the boiling point organic solvent less than 70 DEG C is any one in t-butyl methyl ether, acetone, normal hexane and dichloromethane, preferably dichloromethane.
Assay method the most according to claim 3, it is characterised in that detection method described in step C is direct injected gas chromatography.
Assay method the most according to claim 1, it is characterized in that, the chromatographic column model of described gas chromatograph is: 6% cyanogen propyl group phenyl-94% dimethyl polysiloxane is the capillary column of fixative, the column length 30m of this quartz capillary column, internal diameter 0.32mm, thickness of liquid film 3 μm.
Assay method the most according to claim 4, it is characterised in that the gas chromatogram column condition of direct-injection technique is:
Column temperature: temperature programming；
Injector temperature: 60～75 DEG C；
Flame ionization detector temperature: 180～250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.2～3.2ml/min；
Split ratio: 5:1～15:1.
Assay method the most according to claim 6, it is characterised in that gas chromatogram column condition is:
Column temperature: temperature programming method is that initial temperature 60 DEG C keeps 2 minutes, then with the ramp of 15 DEG C per minute to 200 DEG C, keeps 5 minutes；
Injector temperature: 70 DEG C；
Flame ionization detector temperature: 250 DEG C；
Carrier gas: nitrogen；
Flow rate of carrier gas: 2.7ml/min；
Split ratio: 10:1.
8. according to the application in n-amyl alcohol content in detection capecitabine finished product of the assay method according to any one of claim 1-7.
9. the checking linear test of assay method as claimed in claim 1, comprises the steps:
1) taking n-amyl alcohol appropriate, accurately weighed, the dichloromethane solution containing n-amyl alcohol 0.5mg/ml is made in dilution；
2) precision pipettes 0.2ml, 0.5ml, 1ml, 1.2ml, 1.5ml in 10ml volumetric flask respectively, uses dchloromethane constant volume, shakes up, standby；
3) precision measures step 2 respectively) in each 2 μ l sample introductions of sample, direct injected, record chromatogram；
4) with concentration as x-axis, peak area is y-axis, makees linear regression.
10. the checking recovery test of assay method as claimed in claim 1, comprises the steps:
1) taking n-amyl alcohol appropriate, accurately weighed, dilution makes the dichloromethane solution containing n-amyl alcohol 0.5mg/ml as stock solution；
2) this product about 0.1g is taken, accurately weighed, put in 10ml volumetric flask, add q. s. methylene chloride and make dissolving, precision measures 0.8ml respectively, and 1ml, 1.2ml contrast solution is in 10ml volumetric flask, and add methylene chloride dilution constant volume.Direct injected, records chromatogram；
3) another precision measures 1ml stock solution in the volumetric flask of 10ml, adds methylene chloride and is diluted to scale, shake up, be measured in the same method, calculates its response rate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308274.6A CN105823845B (en) | 2016-05-11 | 2016-05-11 | The measure of capecitabine and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308274.6A CN105823845B (en) | 2016-05-11 | 2016-05-11 | The measure of capecitabine and its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105823845A true CN105823845A (en) | 2016-08-03 |
| CN105823845B CN105823845B (en) | 2018-06-12 |
Family
ID=56528650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610308274.6A Active CN105823845B (en) | 2016-05-11 | 2016-05-11 | The measure of capecitabine and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105823845B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108828077A (en) * | 2018-03-13 | 2018-11-16 | 中国人民解放军第二军医大学第二附属医院 | It is a kind of while detecting the kit and its detection method of capecitabine and its metabolite and application in blood plasma |
| CN110398555A (en) * | 2018-04-24 | 2019-11-01 | 重庆圣华曦药业股份有限公司 | A kind of detection method of the capecitabine in relation to substance |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102199180A (en) * | 2011-04-12 | 2011-09-28 | 连云港杰瑞药业有限公司 | Preparation method of capectabine |
| CN102206239A (en) * | 2010-03-29 | 2011-10-05 | 上海医药工业研究院 | Preparation method of capecitabine |
| CN103288905A (en) * | 2012-02-22 | 2013-09-11 | 北京博时安泰科技发展有限公司 | Novel technology for synthesis of capecitabine |
-
2016
- 2016-05-11 CN CN201610308274.6A patent/CN105823845B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206239A (en) * | 2010-03-29 | 2011-10-05 | 上海医药工业研究院 | Preparation method of capecitabine |
| CN102199180A (en) * | 2011-04-12 | 2011-09-28 | 连云港杰瑞药业有限公司 | Preparation method of capectabine |
| CN103288905A (en) * | 2012-02-22 | 2013-09-11 | 北京博时安泰科技发展有限公司 | Novel technology for synthesis of capecitabine |
Non-Patent Citations (2)
| Title |
|---|
| 左家信等: "HPLC法测定卡培他滨的含量及有关物质", 《海峡药学》 * |
| 益磊等: "卡培他滨中有机残留溶剂的检测", 《中南药学》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108828077A (en) * | 2018-03-13 | 2018-11-16 | 中国人民解放军第二军医大学第二附属医院 | It is a kind of while detecting the kit and its detection method of capecitabine and its metabolite and application in blood plasma |
| CN108828077B (en) * | 2018-03-13 | 2021-10-22 | 中国人民解放军第二军医大学第二附属医院 | Kit for simultaneously detecting capecitabine and metabolite thereof in blood plasma as well as detection method and application thereof |
| CN110398555A (en) * | 2018-04-24 | 2019-11-01 | 重庆圣华曦药业股份有限公司 | A kind of detection method of the capecitabine in relation to substance |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105823845B (en) | 2018-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110320293B (en) | Method for determining residual solvent in phthalide compound | |
| CN104655751B (en) | A kind of detect the method for organic solvent residual in dapoxetine | |
| CN105203658B (en) | The detection method of residual solvent in a kind of Ezetimibe | |
| CN103487541A (en) | Method for simultaneously detecting multiple residual solvents in ceftriaxone sodium | |
| CN105388223B (en) | The assay method of residual solvent in a kind of Decitabine intermediate | |
| CN105717230A (en) | Method for detecting residual organic solvent in Favipiravir | |
| CN104950052A (en) | Method for dementholized peppermint oil dropping pill quality detection by using gas chromatograph | |
| WO2023124924A1 (en) | Method for detecting residual solvent in pingyangmycin hydrochloride bulk drug | |
| CN109765313A (en) | A kind of detection method of fenofibrate choline | |
| CN105823845B (en) | The measure of capecitabine and its application | |
| CN103115969A (en) | Method for determining residual quantities of organic solvents in temozolomide hexyl ester | |
| CN111487340A (en) | Method for detecting organic residual solvent in obeticholic acid raw material medicine | |
| Siddiqui et al. | Determination of residual solvents in docetaxel by headspace gas chromatography | |
| CN112557571B (en) | Quantitative detection method for acryloyl chloride in preparation process of ibrutinib bulk drug | |
| CN106198819B (en) | The method of residual solvent in Headspace Gas Chromatography Xi Gelieting bulk pharmaceutical chemicals | |
| CN105136921A (en) | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate | |
| CN115166080B (en) | Method for detecting impurity A and impurity B in ifosfamide bulk drug | |
| CN102901784A (en) | Method for performing headspace gas chromatographic detection on formic acid in aceclofenac bulk pharmaceutical chemicals | |
| CN108760951A (en) | A method of a variety of residual organic solvents in detection Bioabsorbable Polyesters film | |
| CN107677737A (en) | A kind of method that chloroform is remained in detection Tretinoin | |
| CN109765317B (en) | Composition and detection method of related substances in tofacitinib citrate | |
| CN112630346B (en) | Quantitative analysis method for residual solvent in ibrutinib | |
| CN113092607A (en) | Detection method for residual solvent in loratinib raw material medicine | |
| CN105403635B (en) | The detection method of residual solvent trichloro ethylene in propane diols | |
| CN107894474A (en) | The method that gas chromatography detects hydroxychloroquine side chain and its raw material and intermediate simultaneously |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |