CN106501388A - A kind of method of trichloroacetamide in use gas chromatography separation determination eplerenone - Google Patents
A kind of method of trichloroacetamide in use gas chromatography separation determination eplerenone Download PDFInfo
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- CN106501388A CN106501388A CN201610841820.2A CN201610841820A CN106501388A CN 106501388 A CN106501388 A CN 106501388A CN 201610841820 A CN201610841820 A CN 201610841820A CN 106501388 A CN106501388 A CN 106501388A
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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
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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Abstract
The invention belongs to analytical chemistry field, the invention discloses a kind of method of use gas chromatography quick separating detection eplerenone about material trichloroacetamide, the method adopts methyl polysiloxane class low pole capillary chromatographic column, electron capture detector, the content of trichloroacetamide in eplerenone can be quantitative determined, so as to reach the effective control to eplerenone purity, the quality controllable of eplerenone is realized.The inventive method specificity is strong, and the degree of accuracy is high, and durability is good and simple and quick.
Description
Technical field
The invention belongs to analytical chemistry field, and in particular to trichloroacetamide in gas chromatography separation determination eplerenone
Method.
Background technology
Eplerenone is a kind of new selective aldosterone receptor antagonist, acts only on mineralcorticoid receptor, to hero
The affinity of hormone and progesterone receptor is extremely low, is clinically used for treating hypertension, heart failure and myocardial infarction.Eplerenone
Chemistry is entitled：9,11α-Epoxy-7α-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-
Carbolactone, molecular formula are C24H30O6.
The bad reaction that medicine is produced in Clinical practice except relevant with the pharmacologically active of medicine itself, sometimes with medicine
Present in impurity also have much relations, be the quality and safety for ensureing medicine, register the requirements for pharmaceuticals declared to its technique
During introduce impurity studied and effective control.The organic impurities introduced in synthesizing eplerenone technique has tribromo-acetyl
Amine, its molecular formula are C2H2Cl3NO, structural formula is：
.
Select suitable analysis method, exactly separate and determine eplerenone in impurity trichloroacetamide, to improve according to
Puli's ketone quality, ensure that drug safety has great importance.
Content of the invention
It is an object of the invention to provide the organic impurities trichlorine introduced in a kind of separation, detection synthesizing eplerenone technique
The method of acetamide, so that reach the effective control to eplerenone purity and quality, it is ensured that the quality of eplerenone and medication
Security.
1. a kind of separation of the present invention, determine eplerenone about material method, be to adopt gas chromatographic analysis
Sample is dissolved by technology from suitable solvent, according to the formation and physic-chemical property of impurity to be analyzed, from methyl polysiloxane
Class chromatographic column and electron capture detector.
Above-mentioned described solvent can be the one kind or several in ethanol, methyl alcohol, dichloromethane or DMF
Kind.
Above-mentioned described chromatographic column is selected from brands such as Agilent, Supelco, Phenomenex or Restek.
Above-mentioned described chromatographic column is low pole or the polysiloxane-based capillary chromatographic column of middle grade.
Method of separating and assaying of the present invention, can be realized in accordance with the following methods：
1）Take eplerenone in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing eplerenone 100mg, as confession examination
Product solution；Separately take trichloroacetamide in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing 6 μ g of trichloroacetamide, as
Reference substance solution.
2）Arrange injector temperature be 250 ~ 300 DEG C, flow rate of carrier gas be 0.8 ~ 1.2mL/min, programmed temperature method, intensification journey
Sequence is 100 °C of initial temperature, and with 10 ~ 30 °C per minute of heating rate to 200 °C, 2 ~ 5min of constant temperature, detector temperature are 280
~ 320 DEG C, split ratio is 10:1~50:1.
3）Take 1）Middle need testing solution and each 0.8～3 μ L of reference substance solution, by 2）Chromatographic condition, inject gas-chromatography
Instrument, the content that trichloroacetamide in eplerenone is calculated using external standard method.Wherein：
The model of gas chromatograph, has no special requirements, and the gas chromatograph that the present invention is adopted is for Shimadzu（2010 plus）Gas phase color
Spectrometer
Detector：Electron capture detector；
Chromatographic column：8 CB capillary chromatographic columns of CP-Sil（30m*0.32mm, 1.00 μm）；
Injector temperature：280℃；
Detector temperature：300℃；
Carrier gas（Nitrogen）Flow velocity：1.0mL/min；
Split ratio：50:1；
Sampling volume：1μL
Column temperature rise program：
.
The present invention adopts gas chromatography, from methyl polysiloxane class low pole capillary chromatographic column（30m*0.32mm,
1.00μm）, can fast and effeciently trichloroacetamide in separation determination eplerenone, solve in synthesizing eplerenone technique and introduce
Organic impurities trichloroacetamide separation determination problem, so as to reach the effective control to eplerenone purity.As a result see attached
Fig. 1 ~ 6.
Description of the drawings
Solvent when Fig. 1 is embodiment 1（Absolute ethyl alcohol）Gas chromatogram；
The gas chromatogram of eplerenone when Fig. 2 is embodiment 1；
The gas chromatogram of trichloroacetamide when Fig. 3 is embodiment 1；
The eplerenone sample gas chromatogram of trichloroacetamide is added when Fig. 4 is embodiment 1；
The gas chromatogram of trichloroacetamide when Fig. 5 is embodiment 2；
The gas chromatogram of trichloroacetamide when Fig. 6 is embodiment 3.
Specific embodiment：
Following examples are used for further understanding the present invention, but are not limited to the scope of this enforcement.Below by way of example forms, to this
In the eplerenone that invention is related to, trichloroacetamide detection method is described in further detail, but this should not be interpreted as this
The scope of bright above-mentioned theme is only limitted to Examples below, and all technology that is realized based on the above of the present invention belong to the present invention
Scope.
Embodiment 1
Instrument and condition
Chromatograph：2010 plus gas chromatographs of Shimadzu；
Detector：Electron capture detector；
Chromatographic column：8 CB capillary chromatographic columns of CP-Sil（30m*0.32mm, 1.00 μm）；
Injector temperature：280℃；
Detector temperature：300℃；
Carrier gas（Nitrogen）Flow velocity：1.0mL/min；
Split ratio：50:1；
Sampling volume：1μL
Column temperature rise program：
.
Experimental procedure
Take eplerenone in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing eplerenone 100mg, as according to Puli
Ketone sample solution；Take trichloroacetamide in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing 6 μ g of trichloroacetamide, makees
For reference substance solution；Absolute ethyl alcohol is separately taken as blank solution.It is analyzed by above-mentioned chromatographic condition, records chromatogram, by outer
Mark method is with the content of trichloroacetamide in calculated by peak area eplerenone.As a result see accompanying drawing 1 ~ 4, Fig. 1 is blank solution chromatogram；
Fig. 2 is eplerenone sample solution chromatogram.In Fig. 3, the chromatographic peak of retention time 6.351min is trichloroacetamide.
Fig. 4 is the eplerenone sample gas chromatogram for adding trichloroacetamide.Fig. 1 ~ Fig. 4 shows：The present invention is provided
Method can fast and effeciently trichloroacetamide in separation determination eplerenone, it is possible to accurately carry out quantitative determination, so as to reach
To eplerenone purity and the effective control of quality.
Embodiment 2
Instrument and condition
Chromatograph：2010 plus gas chromatographs of Shimadzu；
Detector：Electron capture detector；
Chromatographic column：8 CB capillary chromatographic columns of CP-Sil（30m*0.32mm, 1.00 μm）；
Injector temperature：285℃；
Detector temperature：300℃；
Carrier gas（Nitrogen）Flow velocity：1.0mL/min；
Split ratio：50:1；
Sampling volume：1μL
Column temperature rise program：
.
Experimental procedure
Take trichloroacetamide appropriate, plus anhydrous alcohol solution makes the solution containing 6 μ g of trichloroacetamide in every 1ml, as right
According to product solution；Absolute ethyl alcohol is separately taken as blank solution.It is analyzed by above-mentioned chromatographic condition, records chromatogram.As a result see attached
In Fig. 5, Fig. 5, the chromatographic peak of retention time 6.363min is trichloroacetamide.
Embodiment 3
Instrument and condition
Chromatograph：2010 plus gas chromatographs of Shimadzu；
Detector：Electron capture detector；
Chromatographic column：8 CB capillary chromatographic columns of CP-Sil（30m*0.32mm, 1.00 μm）；
Injector temperature：280℃；
Detector temperature：300℃；
Carrier gas（Nitrogen）Flow velocity：1.1mL/min；
Split ratio：50:1；
Sampling volume：1μL
Column temperature rise program：
.
Experimental procedure
Take trichloroacetamide appropriate, plus anhydrous alcohol solution makes the solution containing 6 μ g of trichloroacetamide in every 1ml, as right
According to product solution；Absolute ethyl alcohol is separately taken as blank solution.It is analyzed by above-mentioned chromatographic condition, records chromatogram.As a result see attached
In Fig. 6, Fig. 6, the chromatographic peak of retention time 6.010min is trichloroacetamide.
The present invention is verified to the following items of trichloroacetamide analysis method in the eplerenone：
System suitability is tested
Eplerenone and appropriate trichloroacetamide is taken, anhydrous alcohol solution sample is used respectively, is configured to containing eplerenone and trichlorine
The test liquid of acetamide.Gas chromatographic analysis is carried out by the chromatographic condition of embodiment 1, chromatogram is recorded.From Fig. 1 ~ Fig. 4,
Between trichloroacetamide and adjacent peak, separating degree is good with this understanding, and solvent and eplerenone other impurities do not disturb trichlorine
The measure of acetamide.
Sample introduction replica test
By the relevant material trichloroacetamide test liquid of eplerenone, by the chromatographic condition of embodiment 1, repeat sample introduction 6 times, investigate
The repeatability of method.Can be added by result, the method sample introduction repeatability is good.
.
Quantitative limit, test limit
The relevant material trichloroacetamide for taking eplerenone is appropriate, accurately weighed, uses anhydrous alcohol solution sample respectively, is configured to
The test liquid of response, then precision measures that test liquid is appropriate, stepwise dilution is investigated by the chromatographic condition sample introduction of embodiment 1.Three chloroethenes
Acid amides quantitative limit and test limit data are as shown in the table：
.
Linearly
The relevant material trichloroacetamide for taking eplerenone is appropriate, accurately weighed, respectively with anhydrous alcohol solution, is configured to trichlorine
Acetamide stock solution；Precision measures trichloroacetamide stock solution, is diluted to 1% respectively（About quantitative limit concentration）、50%、80%、
The trichloroacetamide need testing solution of 100% and 120% limit concentration, each solution is investigated by the chromatographic condition sample introduction of embodiment 1,
As a result see the table below：
.
The degree of accuracy
The relevant material trichloroacetamide for taking eplerenone is appropriate, accurately weighed, respectively with anhydrous alcohol solution, is configured to trichlorine
Acetamide stock solution；Precision measures trichloroacetamide stock solution in right amount, is diluted with absolute ethyl alcohol, is made into 80%, 100% and respectively
The accuracy test solution of 120% limit concentration.Eplerenone about 100mg is taken, dense with the limit of above-mentioned 80%, 100% and 120% respectively
The accuracy test solution 1mL dissolvings of degree, used as 80%, 100% and 120% need testing solution, each concentration level need testing solution is put down
Row prepares 3 parts；Eplerenone about 100mg is separately taken, 1mL anhydrous alcohol solutions is added, as blank sample solution.Will be above-mentioned molten
Liquid is investigated by the chromatographic condition sample introduction of embodiment 1, and Fig. 4 is 100% need testing solution（Trichloroacetamide is added i.e. in eplerenone）
Chromatogram, retention time is trichloroacetamide for the chromatographic peak of 6.343min, and sample introduction result see the table below：
.
Durability
By finely tuning injector temperature, flow rate of carrier gas, detector temperature and chromatographic column brand isochromatic spectrum condition, we further examine
The durability of method is examined.As a result find, chromatographic column, injector temperature change ± 5 DEG C, carrier gas stream of the method to different brands
Good tolerance under the conditions of speed change ± 0.1mL/min, ± 5 DEG C of detector temperature change etc..In different brands chromatographic column, difference
Under the conditions of injector temperature, flow rate of carrier gas and detector temperature, trichloroacetamide retention time is without significant changes, and can reach
Efficiently separate.
Claims (7)
1. method of a kind of utilization gas chromatography separation detection eplerenone about material trichloroacetamide, it is characterised in that：
From suitable solvent by sample and tribromo-acetyl amine solvent, according to the formation and physic-chemical property of impurity to be analyzed, from methyl
Polysiloxane-based chromatographic column and electron capture detector.
2. method of separating and assaying according to claim 1, solvent can be ethanol, methyl alcohol, dichloromethane or N, N- diformazan
One or more in base formamide.
3. method of separating and assaying according to claim 1, chromatographic column selected from brand be Agilent, Supelco,
The chromatographic column of Phenomenex or Restek.
4. method of separating and assaying according to claim 1, chromatographic column are low pole or middle grade methyl polysiloxane class
Capillary chromatographic column.
5. method of separating and assaying according to claim 1, it is characterised in that including following step：
1) take eplerenone in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing eplerenone 100mg, as confession examination
Product solution；Separately take trichloroacetamide in right amount, plus anhydrous alcohol solution makes the solution in every 1ml containing 6 μ g of trichloroacetamide, as
Reference substance solution；
2）It is 250 ~ 300 DEG C to arrange injector temperature, and flow rate of carrier gas is 0.8 ~ 1.2mL/min, programmed temperature method, and heating schedule is
100 °C of initial temperature, with 10 ~ 30 °C per minute of heating rate to 200 °C, 2 ~ 5min of constant temperature, detector temperature are 280 ~ 320
DEG C, split ratio is 10:1~50:1；
3）Take 1）Middle need testing solution and each 0.8～3 μ L of reference substance solution, by 2）Chromatographic condition, inject gas chromatograph, adopt
The content that trichloroacetamide in eplerenone is calculated with external standard method.
6. method for separating and analyzing according to claim 5, step 2）Described carrier gas is nitrogen or helium.
7. method for separating and analyzing according to claim 5, step 2）Described programmed temperature method, preferably following intensification journey
Sequence：
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112763612A (en) * | 2020-12-28 | 2021-05-07 | 北京诺康达医药科技股份有限公司 | Detection method of halogenated amide substances |
| CN114965778A (en) * | 2022-05-30 | 2022-08-30 | 江西威科油脂化学有限公司 | Method for determining palmitamide and stearamide in stearamide product |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112763612A (en) * | 2020-12-28 | 2021-05-07 | 北京诺康达医药科技股份有限公司 | Detection method of halogenated amide substances |
| CN114965778A (en) * | 2022-05-30 | 2022-08-30 | 江西威科油脂化学有限公司 | Method for determining palmitamide and stearamide in stearamide product |
| CN114965778B (en) * | 2022-05-30 | 2023-11-17 | 江西威科油脂化学有限公司 | Determination method of palmitoyl acid amide and stearic acid amide in stearic acid amide product |
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Application publication date: 20170315 |