CN111380982B - Method for detecting content of 2-chloroethanol in cloperamide hydrochloride raw material - Google Patents
Method for detecting content of 2-chloroethanol in cloperamide hydrochloride raw material Download PDFInfo
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Abstract
The invention belongs to the field of medicines, and particularly relates to a method for detecting the content of 2-chloroethanol in a chloropipedine hydrochloride raw material. The method adopts 3-15% acetic acid aqueous solution as a sample solvent, adopts a head space sample injection method through a GC-MS method, can accurately detect the content of 2-chloroethanol in the chloropipedine hydrochloride raw material, and has a recovery rate of over 90%.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a method for detecting the content of 2-chloroethanol in a chloropipedine hydrochloride raw material.
Background
Cloperastine hydrochloride (cloperastine hydrochloride) with the chemical name of 1- [2- [ (4-chloro-alpha-phenyl benzyl) oxy ] ethyl ] piperidine hydrochloride is an analogue of diphenhydramine, can inhibit the cough center, and is mainly used for treating dry cough clinically without dependence and tolerance. The synthesis of the cloperamide hydrochloride needs to use 2-chloroethanol as a raw material, and the 2-chloroethanol has genotoxicity, so that the control and analysis of the 2-chloroethanol content in the cloperamide hydrochloride raw material are necessary.
According to the EMEA genotoxic impurity limit study guidelines and ICH Q3 related regulations, an acceptable intake of 1.5 μ g per day using TTC is calculated according to strict rules of genotoxic impurity control and a maximum daily dosage of cloperadine hydrochloride of 60mg, thus a limit of 2-chloroethanol of 25ppm. Referring to the domestic and foreign pharmacopoeia and related data, the existing 2-chloroethanol detection method mainly comprises a Gas Chromatography (GC) method and a gas chromatography-mass spectrometry (GC-MS) method, and because the limit of the 2-chloroethanol is lower, the sensitivity of the GC method cannot meet the requirement. The inventor discovers that the sample injection needle and the chromatographic column of the 2-chloroethanol have strong adsorbability when the GC-MS method is used for measuring the 2-chloroethanol in the chloropiperdine hydrochloride raw material, the needle is easy to block by direct injection, the residual effect of the chromatographic column is obvious, and when the headspace method is used for injection, the sample chloropiperdine hydrochloride has obvious matrix effect on the measurement of the 2-chloroethanol and the recovery rate is less than 60 percent, so that the method for accurately and conveniently detecting the content of the 2-chloroethanol in the chloropiperdine hydrochloride raw material has important significance.
Technical content
The invention aims to provide a method for detecting the content of 2-chloroethanol in a chloropipedine hydrochloride raw material, which adopts 3-15% of acetic acid aqueous solution as a sample solvent, can accurately detect the content of 2-chloroethanol in the chloropipedine hydrochloride raw material by a GC-MS method, and has the recovery rate of more than 90%.
In order to achieve the purpose, the invention provides the following technical scheme:
a method for detecting the content of 2-chloroethanol in a chloropipedine hydrochloride raw material comprises the following steps:
(1) Taking 3% -15% acetic acid water solution as solvent, preparing a cloperamide hydrochloride test solution and a 2-chloroethanol reference solution;
(2) The capillary column with polyethylene glycol (or similar polarity) as stationary liquid is used as chromatographic column, EI is used as detector, headspace sampling is carried out, the 2-chloroethanol peak areas in the cloperamide hydrochloride test solution and the 2-chloroethanol reference solution are determined by adopting GC-MS method, and the 2-chloroethanol content in the test solution is calculated according to external standard method.
According to the invention, the solvent is a 5% -10% aqueous acetic acid solution; further, the solvent is an 8% acetic acid aqueous solution.
According to the invention, the concentration of the test solution of the cloperamide hydrochloride is 0.05g/ml to 0.15g/ml, and further, the concentration of the test solution of the cloperamide hydrochloride is 0.1g/ml.
According to the invention, the concentration of the 2-chloroethanol control solution is 150% -50% of the limit concentration, further, the concentration of the 2-chloroethanol control solution is the limit concentration, and the limit concentration is the concentration of the test sample solution of the cloperamide hydrochloride multiplied by the 2-chloroethanol limit (25 ppm).
According to the invention, the capillary column is an HP-INNOWAX capillary column.
According to the invention, the headspace sampling is to precisely measure a test solution and a reference solution which are equal in volume respectively, place the solutions in a headspace bottle and seal the headspace bottle, wherein the volume is 1ml to 5ml; further, the volume is 1ml.
The method for detecting the content of 2-chloroethanol in the raw material of the cloperamide hydrochloride comprises the following steps:
(1) Using 8% acetic acid water solution as solvent, preparing 0.1g/ml hydrochloric acid cloperadine sample solution and 2-chloroethanol contrast solution with 2.5 mug/ml concentration;
(2) An HP-INNOWAX capillary column is used as a chromatographic column, EI is used as a detector, 1ml of each of the sample solution and the reference solution is precisely measured, the sample solution and the reference solution are placed in a top empty bottle and sealed, the 2-chloroethanol peak areas in the cloperamide hydrochloride sample solution and the 2-chloroethanol reference solution are measured by adopting a GC-MS method, and the 2-chloroethanol content in the sample solution is calculated according to an external standard method.
The GC-MS method has the chromatographic conditions that the initial column temperature is 40 ℃, the temperature is maintained for 2 minutes, the temperature is increased to 160 ℃ at the rate of 15 ℃ per minute, the temperature is increased to 230 ℃ at the rate of 30 ℃ per minute, the temperature is maintained for 1 minute, and the injection port temperature is 250 ℃; the carrier gas is helium, the flow rate is 0.6ml per minute, and the split ratio is 1; the headspace equilibrium temperature is 90 ℃, and the equilibration time is 30 minutes; the mass spectrum conditions comprise ionization voltage of 70eV, ion source temperature of 230 ℃, mass spectrum transmission interface temperature of 250 ℃, MS four-bar temperature of 150 ℃ and solvent delay of 7min; SIM mode, qualitative ion of m/z31, m/z43, m/z80, m/z49, quantitative ion of m/z31.
The inventor finds that the selection of the solvent has great influence on the detection of the content of the 2-chloroethanol in the raw material of the cloperamide hydrochloride, when common solvents such as water, DMF, acetonitrile and the like are used as the solvent, the peak area of the 2-chloroethanol is very small, the detection sensitivity is very low, the recovery rate of a recovery experiment is less than 60 percent, and the RSD is far more than 20 percent; when a salt adding mode such as sodium chloride, sodium dihydrogen phosphate and ammonium sulfate is adopted, the detection sensitivity can be improved, but the recovery rate is only about 70 percent, the requirement cannot be met, and the RSD value is also large. The inventor unexpectedly finds that when the acetic acid aqueous solution with the concentration of more than 3% is used as the solvent, the detection sensitivity can be effectively improved, and the recovery rate can reach more than 80%; along with the increase of the concentration of the aqueous acetic acid solution, the recovery rate is increased, when the concentration of the aqueous acetic acid solution is 8%, the recovery rate can reach 93%, when the concentration of the aqueous acetic acid solution exceeds 15%, the recovery rate can approach 95%, considering the influence of a solvent on a gas chromatograph, the aqueous acetic acid solution with the concentration of 3% -15% is preferred, and the aqueous acetic acid solution with the concentration of 8% is preferred.
The inventor also finds that the concentration of the test solution of the clopidogrel hydrochloride is too high, the matrix effect is increased, the concentration is too low, the detection sensitivity of the 2-chloroethane is too low, and when the concentration is 0.05g/ml-0.15g/ml, particularly 0.1g/ml, the recovery rate requirement can be met, and the detection sensitivity is also high.
Drawings
FIG. 1 is a test chart of a test solution of example 1;
FIG. 2 is a detection chart of a control solution of example 1;
figure 3 is a detection scheme of a blank solution of example 1.
Detailed Description
The instrument used by the invention is an Agilent GCMS-5977B gas chromatograph which is provided with a PE Turbomatrix 40 headspace sample injector; agilent HP-INNOWAX (0.25 mm. Times.30m, 1.8 μm) capillary column; quintix224-1CN electronic balance; the used reagents are 2-chloroethanol reference substances (sold on the market, the content is 100%), cloperadine hydrochloride raw material medicines (sold on the market), and the rest reagents are commercially available analytical reagents.
EXAMPLE 1 content measurement of chloroethanol
Precisely weighing 25.58mg of 2-chloroethanol reference substance, placing into a 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to a scale, shaking up, precisely weighing 1ml, placing into a 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to a scale, shaking up to obtain a reference solution with the concentration of 2.56 mu g/ml; precisely weighing 1.003g of the product, putting the product into 10ml of the product, adding 8% acetic acid aqueous solution for dissolving, diluting to a scale, and shaking uniformly to obtain a test solution; 8% acetic acid water solution is used as a blank solvent. Precisely measuring 1ml of each of the control solution, the test solution and the blank solvent, placing in a headspace bottle, sealing, and sampling with Agilent HP-INNOWAX (0.25 mm × 30m,1.8 μm) capillary column as capillary column. The gas chromatography conditions adopted are that the initial column temperature is 40 ℃, the temperature is maintained for 2 minutes, the temperature is increased to 160 ℃ at the rate of 15 ℃ per minute, the temperature is increased to 230 ℃ at the rate of 30 ℃ per minute, the temperature is maintained for 1 minute, and the injection port temperature is 250 ℃; the carrier gas is helium, the flow rate is 0.6ml per minute, and the split ratio is 1. The headspace sampling condition adopted the headspace equilibrium temperature of 90 ℃ and the equilibrium time of 30 minutes. The mass spectrum condition adopts an Electron Impact (EI) source, the ionization voltage is 70eV, the ion source temperature is 230 ℃, the mass spectrum transmission interface temperature is 250 ℃, the MS four-bar temperature is 150 ℃, and the solvent delay is 7min; SIM mode, qualitative ion is m/z31, m/z43, m/z80, m/z49, quantitative ion is m/z31.
The results are shown in FIGS. 1, 2 and 3, and no 2-chloroethanol was detected in the samples.
Example 2 Linear test
Precisely weighing 25.58mg of 2-chloroethanol reference substance, placing the reference substance into a 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to a scale, shaking up, precisely weighing 1ml, placing the reference substance into the 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to the scale, shaking up to obtain a reference solution with the concentration of 2.56 mu g/ml, and sequentially diluting by 2 times to prepare series of reference solutions with the concentrations of 1.28 mu g/ml, 0.64 mu g/ml, 0.32 mu g/ml, 0.16 mu g/ml and 0.08 mu g/ml. Precisely measuring 1ml of a series of control solutions, placing the solutions in a headspace bottle, sealing, and recording a chromatogram. And extracting an ion chromatogram of m/z31, and calculating a regression equation by taking the peak area of 2-chloroethanol as a vertical coordinate (Y) and the concentration of 2-chloroethanol as a horizontal coordinate (X). The result shows that the 2-chloroethanol has good linear relation in the concentration range of 0.08-2.56 mug/ml, the correlation coefficient is 0.9998, the detection Limit (LOD) is 22ng/ml and the quantification Limit (LOQ) is 73ng/ml according to the signal-to-noise ratio of 3 and 10. The results are shown in Table 1.
TABLE 1
EXAMPLE 3 repeatability test
1ml of a control solution having a concentration of 2.56. Mu.g/ml was precisely measured, and placed in a headspace bottle, 6 parts in total, and measured under the conditions of example 1, and a chromatogram was recorded, and the results showed that RSD of 2-chloroethanol retention time was 0.18% and RSD of 2-chloroethanol peak area was 1.8% (n = 6), and the results were shown in table 2.
TABLE 2
Example 4 recovery test
Precisely weighing 25.58mg of 2-chloroethanol reference substance, placing the reference substance into a 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to a scale, shaking up, precisely weighing 1ml, placing the reference substance into the 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to the scale, shaking up to obtain a reference solution with the concentration of 2.56 mu g/ml, precisely weighing a proper amount of the reference solution, and quantitatively diluting with 8% acetic acid aqueous solution to obtain a reference solution containing 1.54 mu g/ml of 2-chloroethanol and 1.02 mu g/ml in each 1ml. Precisely weighing 1g of 3 parts of the same batch of cloperamide hydrochloride raw material (190720), placing the same batch of cloperamide hydrochloride raw material into a 10ml measuring flask, respectively adding control solutions with the concentrations of 2.56 mu g/ml, 1.54 mu g/ml and 1.02 mu g/ml, dissolving and diluting the control solutions to scales, shaking the solutions evenly, precisely weighing 1ml, placing the solutions into a top empty flask, respectively weighing 3 parts of the reference solutions, totally 9 parts of the reference solutions, sealing the solutions, measuring the conditions according to the example 1, recording a chromatogram, calculating the recovery rate according to an external standard method, wherein the result shows that the average recovery rate of chloroethane is 92.9 percent, the RSD value is 1.8 percent (n = 9), and the method has good accuracy. The results are shown in Table 3.
TABLE 3
EXAMPLE 5 content measurement of chloroethanol
Precisely weighing 25.32mg of 2-chloroethanol reference substance, placing the reference substance in a 100ml measuring flask, adding 5% acetic acid aqueous solution to dilute to a scale, shaking up, precisely weighing 1ml, placing the reference substance in the 100ml measuring flask, adding 5% acetic acid aqueous solution to dilute to the scale, and shaking up to obtain a reference solution with the concentration of 2.53 mu g/ml; accurately weighing 1.1125g of the product, placing into 10ml of the product, adding 5% acetic acid water solution to dissolve and dilute to scale, shaking uniformly to obtain a test solution; 5% acetic acid water solution is used as a blank solvent. Precisely measuring 1ml of each of the reference solution, the test solution and the blank solvent, placing the reference solution, the test solution and the blank solvent in a top empty bottle, sealing the top empty bottle, and detecting the contents of the reference solution, the test solution and the blank solvent by the method in the embodiment 1, wherein 2-chloroethanol is not detected in a sample.
EXAMPLE 6 content measurement of 2-chloroethanol
Precisely weighing 25.58mg of 2-chloroethanol reference substance, placing into a 100ml measuring flask, adding 8% acetic acid aqueous solution to dilute to a scale, shaking up, precisely weighing 1ml, placing into a 100ml measuring flask, adding 10% acetic acid aqueous solution to dilute to a scale, shaking up to obtain a reference solution with the concentration of 2.56 mu g/ml; accurately weighing 1.1870g of the product, placing into 10ml, adding 10% acetic acid water solution to dissolve and dilute to scale, shaking to obtain test solution; 10% acetic acid water solution is used as a blank solvent. Precisely measuring the reference solution, the sample solution and the blank solvent by 1ml respectively, placing the reference solution, the sample solution and the blank solvent in a top empty bottle, sealing the top empty bottle, and detecting according to the method of example 1, wherein 2-chloroethanol is not detected in the sample.
Claims (9)
1. A method for detecting the content of 2-chloroethanol in a cloperadine hydrochloride raw material comprises the following steps:
(1) Preparing a clopidogrel hydrochloride test solution and a 2-chloroethanol reference solution by using a 3-15% acetic acid aqueous solution as a solvent, wherein the concentration of the clopidogrel hydrochloride test solution is 0.05g/ml-0.15g/ml;
(2) The capillary column with polyethylene glycol as stationary liquid is used as chromatographic column, EI is used as detector, headspace sampling is carried out, the 2-chloroethanol peak area in the cloperadine hydrochloride test sample solution and the 2-chloroethanol reference solution is determined by adopting GC-MS method, and the 2-chloroethanol content in the test sample solution is calculated according to external standard method.
2. The method of claim 1, wherein: the chromatographic conditions of the GC-MS method are that the initial column temperature is 40 ℃, the initial column temperature is maintained for 2 minutes, the temperature is increased to 160 ℃ at the rate of 15 ℃ per minute, the temperature is increased to 230 ℃ at the rate of 30 ℃ per minute, the initial column temperature is maintained for 1 minute, and the injection port temperature is 250 ℃; the carrier gas is helium, the flow rate is 0.6ml per minute, and the split ratio is 1; the headspace equilibrium temperature is 90 ℃ and the equilibration time is 30 minutes; the mass spectrum conditions comprise ionization voltage of 70eV, ion source temperature of 230 ℃, mass spectrum transmission interface temperature of 250 ℃, MS four-bar temperature of 150 ℃ and solvent delay of 7min; SIM mode, qualitative ion is m/z31, m/z43, m/z80, m/z49, quantitative ion is m/z31.
3. The method of claim 1, wherein: the solvent is 5% -10% acetic acid water solution.
4. The method of claim 1, wherein: the concentration of the test solution of the cloperamide hydrochloride is 0.1g/ml.
5. The method of claim 1, wherein: the capillary column is an HP-INNOWAX capillary column.
6. The method of claim 1, wherein: the headspace sampling is to precisely measure a test solution and a reference solution with equal volumes respectively, place the solutions in a headspace bottle, and seal the headspace bottle, wherein the volume is 1ml to 5ml.
7. The method of claim 1, wherein: the method comprises the following steps:
(1) Using 8% acetic acid water solution as solvent, preparing 0.1g/ml hydrochloric acid cloperadine sample solution and 2-chloroethanol contrast solution with 2.5 mug/ml concentration;
(2) Precisely measuring 1ml of each of a sample solution and a reference solution by taking an HP-INNOWAX capillary column as a chromatographic column and an EI as a detector, placing the sample solution and the reference solution in a headspace bottle, sealing, measuring the 2-chloroethanol peak areas in the cloperamide hydrochloride sample solution and the 2-chloroethanol reference solution by adopting a GC-MS method, and calculating the 2-chloroethanol content in the sample solution according to an external standard method;
the GC-MS method comprises the chromatographic conditions that the initial column temperature is 40 ℃, the initial column temperature is maintained for 2 minutes, the temperature is increased to 160 ℃ at the rate of 15 ℃ per minute, the temperature is increased to 230 ℃ at the rate of 30 ℃ per minute, the initial column temperature is maintained for 1 minute, and the injection port temperature is 250 ℃; the carrier gas is helium, the flow rate is 0.6ml per minute, and the split ratio is 1; the headspace equilibrium temperature is 90 ℃ and the equilibration time is 30 minutes; the mass spectrum conditions are ionization voltage of 70eV, ion source temperature of 230 ℃, mass spectrum transmission interface temperature of 250 ℃, MS four-bar temperature of 150 ℃ and solvent delay of 7min; SIM mode, qualitative ion is m/z31, m/z43, m/z80, m/z49, quantitative ion is m/z31.
8. The method of claim 1, wherein: the solvent is an 8% acetic acid aqueous solution.
9. The method of claim 1, wherein: the headspace sampling is to precisely measure a test solution and a reference solution with equal volumes respectively, place the solutions in a headspace bottle and seal the bottle, wherein the volume is 1ml.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108426958A (en) * | 2018-04-26 | 2018-08-21 | 浙江奇彩环境科技股份有限公司 | A kind of ethylene chlorhydrin headspace gas chromatography-mass spectrometry method in water |
| CN113552230A (en) * | 2020-04-24 | 2021-10-26 | 江苏天士力帝益药业有限公司 | Method for measuring content of chloroethanol in gelatin hollow capsule |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108426958A (en) * | 2018-04-26 | 2018-08-21 | 浙江奇彩环境科技股份有限公司 | A kind of ethylene chlorhydrin headspace gas chromatography-mass spectrometry method in water |
| CN113552230A (en) * | 2020-04-24 | 2021-10-26 | 江苏天士力帝益药业有限公司 | Method for measuring content of chloroethanol in gelatin hollow capsule |
Non-Patent Citations (4)
| Title |
|---|
| Development of chromatographic methods for the determination of genotoxic impurities in cloperastine fendizoate;Antonia García 等;《Journal of Pharmaceutical and Biomedical Analysis》;20111219;第61卷;230-236 * |
| 气相色谱-质谱法测定盐酸氯哌丁原料药中2-氯乙醇的残留量;钟振华 等;《分析试验室》;20180930(第09期);1071-1074 * |
| 脉络宁注射液及吐温80辅料中三种有害杂质的筛选和测定;万晓君 等;《中国药事》;20161231;第30卷(第12期);1289-1297 * |
| 顶空气相色谱法测定空心胶囊的有机残留氯乙醇含量;邱咏梅;《海峡药学》;20041231;第16卷(第4期);77-78 * |
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