CN114264736A - Method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride - Google Patents
Method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride Download PDFInfo
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Abstract
The invention provides a method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride. The method comprises the steps of pretreating a blank solution, a reference solution and a sample solution by a headspace sampler, heating until the gas-liquid balance is achieved, injecting gas above a headspace bottle into a gas chromatograph, carrying out temperature programming, then entering a detector for measuring and recording a corresponding chromatogram so as to determine the content of 1, 2-dichloroethane. The method can be well applied to evaluating the residual quantity of the 1, 2-dichloroethane solvent in the sultopride hydrochloride.
Description
Technical Field
The invention relates to the field of drug analysis, in particular to a method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride.
Background
1, 2-dichloroethane is an organic solvent widely used in industry, is colorless at room temperature, has liquid similar to chloroform gas, is toxic, has a chronic carcinogenic effect, has a great influence on human health, and is also one of the detection indexes of traditional Chinese medicines. The registration of human pharmaceuticals requires that the international harmonization Institute (ICH) allow a residual limit of only 0.0005%. The solvent is avoided in most of the synthetic routes of the raw material medicaments, but 1, 2-dichloroethane is still used as a reaction solvent in part of the synthetic processes of the raw material medicaments.
Sultopride hydrochloride has central dopamine resisting effect. Acts on dopamine D2 receptor, and is dopamine receptor blocker. It has tranquilizing effect, and can be used for inhibiting mania, hallucination, delusion and psychomotor excitation. Compared with chlorpromazine, haloperidol and lithium, the product has the advantages of rapid action, strong action, and little adverse side effect, and is characterized by controlling acute mental excitation state. However, 1, 2-dichloroethane is added as a solvent in the synthetic process of the sultopride hydrochloride, and the limit is 5ppm according to the requirements of pharmacopoeia residual solvent, so that the content of the 1, 2-dichloroethane in the sultopride hydrochloride needs to be detected, and a flame ionization detector is mostly adopted in the prior art at present, and the responsivity is low.
As in the literature: a method for analyzing the residual quantity of ethanol and 1, 2-dichloroethane in the etamsylate (Yibixin, etc., Chinese pharmacist, 2013,16(12):1824-1827) is provided in the determination of the residual quantities of the ethanol and the 1, 2-dichloroethane in the etamsylate by a headspace capillary gas chromatography, but the limit concentration of the 1, 2-dichloroethane in the method is 0.105 mu g/mL, and the sensitivity is low. And no relevant report on the detection technology of the 1, 2-dichloroethane in the sultopride hydrochloride exists at present, so that the establishment of a special and sensitive analysis method for measuring the 1, 2-dichloroethane content in the sultopride hydrochloride and effectively controlling the quality of the sultopride hydrochloride is a problem to be solved urgently by a person skilled in the art.
Disclosure of Invention
The invention provides a method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride, aiming at the problems in the prior art. The method has strong applicability and high sensitivity, can accurately analyze the content of 1, 2-dichloroethane in the sultopride hydrochloride, and provides a high-efficiency quality control method for the sultopride hydrochloride medicine so as to ensure the safety of the sultopride hydrochloride medicine.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the invention firstly provides a method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride, which comprises the steps of analyzing the sultopride hydrochloride by gas chromatography to obtain a chromatogram map so as to determine the content of 1, 2-dichloroethane; the method specifically comprises the following steps:
(1) preparing a blank solution, a control solution and a test solution;
(2) pretreating the blank solution, the reference solution and the sample solution by adopting a headspace sampler, heating until the gas-liquid balance is achieved, injecting gas above a headspace bottle into a gas chromatograph, and analyzing the sultopride hydrochloride by using the gas chromatography to obtain a chromatogram so as to determine the content of the 1, 2-dichloroethane.
The quality control and detection of the sultopride hydrochloride are technical problems in the field, and the known technical problems in the field are that the detection results are greatly different aiming at the micro design changes in the same medicine quality control method; in addition, for different medicines and preparations, chemical components in the medicines are different, and slightly different medicinal components can cause the impurity components in the detection of the 1, 2-dichloroethane to be greatly different, so that the detection accuracy is influenced, and therefore, the detection method of the 1, 2-dichloroethane in different medicines or preparations has no reference value. According to the invention, through a large number of experiments, the gas chromatography conditions are groped to finally determine the better conditions suitable for detecting the 1, 2-dichloroethane solvent residue in the sultopride hydrochloride.
Specifically, the blank solution, the reference solution and the sample solution are pretreated by a headspace sampler in the step (2), after the blank solution, the reference solution and the sample solution are heated to be in gas-liquid equilibrium, 1.0mL of gas above a headspace bottle of the blank solution, the reference solution and the sample solution is respectively sucked by a sampling needle and injected into a gas chromatograph for programmed temperature rise, and after the programmed temperature rise is finished, the sample enters a detector for measurement and records a corresponding chromatogram.
Preferably, the blank solution is prepared by: uniformly mixing dimethyl sulfoxide (DMSO) with the same volume with purified water to obtain a blank solution.
More preferably, the blank solution is prepared by: and (3) putting DMSO and purified water with the same volume into a headspace bottle, sealing, and uniformly mixing to obtain a blank solution.
Preferably, the control solution is prepared by: adding DMSO into 1, 2-dichloroethane to dilute to obtain a first control stock solution with 1, 2-dichloroethane concentration of 1.25 mg/mL; adding DMSO into the first control stock solution to dilute 2500 times to obtain a second control stock solution; adding purified water with the same volume as the second control stock solution, and mixing to obtain the control solution.
Specifically, the preparation of the control solution is as follows: adding DMSO into a volumetric flask to dilute the 1, 2-dichloroethane, and mixing uniformly to obtain a first control stock solution with the 1, 2-dichloroethane concentration of 1.25 mg/mL; taking the first control stock solution into a volumetric flask, diluting by 100 times with DMSO, and mixing uniformly to obtain a second control stock solution; taking the second control stock solution into a volumetric flask, diluting the second control stock solution by 25 times with DMSO, and uniformly mixing to obtain a third control stock solution; and (4) taking the third control stock solution into a headspace bottle, adding purified water with the same volume, and sealing to obtain a control solution.
Preferably, the test solution is prepared by: adding DMSO into a test sample to dissolve, adding purified water with the same volume as the DMSO, and mixing uniformly to obtain a test sample solution; the dosage ratio of the test sample to DMSO is 100 mg: 1 mL.
More preferably, the test solution is prepared by: weighing a test sample in a headspace bottle, adding DMSO for dissolving, adding purified water with the same volume as that of the DMSO, sealing, and mixing uniformly to obtain a test sample solution.
Preferably, the gas chromatography conditions are:
headspace injector conditions: the headspace sample injection bottle temperature is 60-65 ℃, the heat preservation time is 25-30 min, the pressurization time is 1.8-2.2 min, the sampling needle temperature is 70-75 ℃, the sample injection time is 0.2-0.3 min, the cycle time is 27-30 min, and the transmission line temperature is 80-85 ℃;
the temperature of a sample inlet is 170-175 ℃, the sample injection amount is 1.0-1.2 mL, and the split ratio is 1: 1-2: 1;
the carrier gas is nitrogen, and the flow rate is 0.45-0.50 mL/min;
temperature programming: the initial temperature is 58-60 ℃, the temperature is increased to 115-120 ℃ at the speed of 9-11 ℃/min after the initial temperature is maintained for 2-3 min, the temperature is increased to 210-220 ℃ at the speed of 28-30 ℃/min, and the initial temperature is maintained for 5-6 min;
a detector: a μ ECD detector;
the temperature of the detector is 250-265 ℃, the tail blowing is 25-30 mL/min, and the sampling frequency is 20-50 Hz;
the chromatographic column is a DB-624 chromatographic column with the model of 30m multiplied by 0.32mm multiplied by 1.8 mu m.
More preferably, the headspace injector conditions are: the headspace sample injection bottle temperature is 60 ℃, the heat preservation time is 30min, the pressurization time is 2min, the sampling needle temperature is 70 ℃, the sample injection time is 0.2min, the cycle time is 27min, the transmission line temperature is 80 ℃, the needle pulling time is 0.4-0.5 min, and the balance pressure is 12-15 psi. The invention controls the temperature of the headspace sample injection bottle under the condition, comprehensively considers the test time and accuracy, the higher the temperature of the headspace sample injection bottle is, the higher the vapor pressure is, the higher the concentration of the headspace gas is, the higher the analysis sensitivity is, but the overhigh temperature can cause the decomposition and oxidation of certain components and can also cause the overhigh pressure of the headspace gas to cause the air leakage of the system.
More preferably, the headspace injector conditions are: needle withdrawal time was 0.4min, and pressure was balanced at 15 psi.
Preferably, the injection port temperature is 170 ℃, and the split ratio is 1: 1. The invention controls the sample feeding amount and the split ratio under the condition, and comprehensively considers the influence on the retention time and the peak area of the sample and the adjacent and close peaks. If the sample amount is too large, the separation efficiency is reduced, and the peak is deformed and smeared, which is not favorable for quantification.
More preferably, the sample size is 1.0 mL.
Preferably, the carrier gas flow rate is 0.50 mL/min. The present invention controls the flow rate of the carrier gas under such conditions in consideration of the influence on the area of the measurement peak of the sample. If the carrier gas flow rate is too high, the peak area is small, and the sensitivity is lowered.
Preferably, the temperature programming: the initial temperature is 60 ℃, the temperature is maintained for 2min, then the temperature is increased to 120 ℃ at the speed of 10 ℃/min, and then the temperature is increased to 220 ℃ at the speed of 30 ℃/min, and the temperature is maintained for 5 min. The invention controls the temperature programming under the condition, and comprehensively considers the influence on the separation and analysis results of the substances. The initial temperature is low enough to separate low boiling point components in the mixture, but too low a temperature will reduce column efficiency and prolong analysis time; the temperature rise rate takes the separation degree and the analysis speed into consideration, and too fast temperature rise is not beneficial to separation, and too slow temperature rise can cause the side length of analysis time.
Preferably, the temperature of the detector is 250 ℃, the tail blowing is 25mL/min, and the sampling frequency is 20-50 Hz. The invention controls tail blowing under the condition, comprehensively considers the influence of an analysis method on the peak type and the sensitivity, leads to serious peak tailing when the tail blowing is too small, and reduces the sensitivity when the flow is too large.
More preferably, the sampling frequency is 20 Hz.
Compared with the prior art, the invention realizes the following beneficial effects:
1. according to the analysis method, the headspace sample introduction pretreatment is carried out on the test sample, the mu ECD detector is adopted for detection, and the content of the 1, 2-dichloroethane solvent in the sultopride hydrochloride is accurately determined.
2. The application selects the mu ECD detector for detection, selects proper temperature programming parameters, has strong detection applicability and high sensitivity, has the limit of quantitative limit of 0.50ppm, meets the requirements of pharmacopoeia, and has better practicability.
Drawings
FIG. 1 is a gas chromatogram of a blank solution;
FIG. 2 is a first needle chromatogram of a control solution of example 1;
FIG. 3 is a second needle gas chromatogram of a control solution of example 1;
FIG. 4 is a third chromatogram of a control solution of example 1;
FIG. 5 is a fourth pin gas chromatogram of a control solution of example 1;
FIG. 6 is a fifth chromatogram of a control solution of example 1;
FIG. 7 is a sixth chromatogram of a control solution of example 1;
FIG. 8 is a sensitive solution gas chromatogram;
FIG. 9 is a first needle chromatogram of a quantitation limit solution;
FIG. 10 is a second needle gas chromatogram of a limiting quantitation solution;
FIG. 11 is a third hand gas chromatogram of a quantitation limit solution;
FIG. 12 is a first needle chromatogram of a sample solution;
FIG. 13 is a second-hand gas chromatogram of a sample solution;
FIG. 14 is a first needle chromatogram of a control solution of example 3;
FIG. 15 is a second needle gas chromatogram of a control solution of example 3;
FIG. 16 is a first needle chromatogram of a sample solution;
FIG. 17 is a second set of gas chromatograms of the sample and the standard solution;
FIG. 18 is a gas chromatogram of a methanol peak belonging solution;
FIG. 19 is a gas chromatogram of an ethanol peak-belonging solution;
FIG. 20 is a gas chromatogram of a dichloromethane peak belonging solution;
FIG. 21 is a gas chromatogram of an ethyl acetate peak-belonging solution;
FIG. 22 is a gas chromatogram of an N, N-dimethylpyrrolidone peak belonging solution;
FIG. 23 is a gas chromatogram of an N, N-dimethylformamide peak-belonging solution;
FIG. 24 is a gas chromatogram of a toluene peak belonging solution.
Detailed Description
The present invention is further described in detail below with reference to specific examples, which are provided for illustration only and are not intended to limit the scope of the present invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
The instruments and reagents involved in the following examples include: gas chromatograph Agilent 7890A-G3440A; electronic analytical balance Mettler-XA 502DU (one hundred thousand); methanol (chromatographically pure, curuder reagent); ethyl acetate (chromatographically pure, alatin reagent shanghai ltd); ethanol (chromatographically pure, merck, germany); dichloromethane (chromatographically pure, Shanghai Kangchi high purity solvent Co., Ltd.); n, N-dimethylformamide (chromatographically pure, kruder reagent); toluene (analytically pure, west longa science ltd); methylpyrrolidone (chromatographically pure, alatin reagent shanghai ltd); dimethyl sulfoxide (chromatographically pure, merck, germany); 1, 2-dichloroethane (chromatographically pure, mclin's reagent), water is purified water.
The test sample, sultopride hydrochloride (batch No. S503A-RD201902101R1), was purchased from Guangdong Dongyang pharmaceutical Co., Ltd.
Example 1 System suitability test
A method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride comprises the following steps:
s1, preparing a blank solution: precisely transferring 1mL of DMSO and 1mL of purified water into a 20mL headspace bottle respectively, sealing, and uniformly mixing to obtain a blank solution;
s2, preparing a first control stock solution: taking 125mg of 1, 2-dichloroethane, putting the 1, 2-dichloroethane in a 100mL volumetric flask, diluting the 1, 2-dichloroethane to a scale with DMSO, and uniformly mixing the diluted 1, 2-dichloroethane and the scale to obtain a first control stock solution with the 1.25mg/mL of 1, 2-dichloroethane;
s3, preparing a second control stock solution: precisely transferring 1mL of the first control stock solution into a 100mL volumetric flask, diluting the first control stock solution to a scale with DMSO, and uniformly mixing the first control stock solution and the DMSO;
s4, preparing a third contrast stock solution: precisely transferring 2mL of the second control stock solution into a50 mL volumetric flask, diluting the second control stock solution to a scale with DMSO, and uniformly mixing the second control stock solution and the DMSO;
s5, preparing a contrast solution: precisely transferring 1mL of the third control stock solution into a 20mL headspace bottle, precisely adding 1mL of purified water, and sealing to obtain the final product;
s6, preparation of a sensitivity solution (30% control solution): precisely transferring 3mL of the third control stock solution into a 10mL volumetric flask, diluting the third control stock solution to a scale with DMSO, uniformly mixing, transferring the solution into a 1mL to 20mL headspace flask, precisely adding 1mL of purified water, sealing, and uniformly mixing to obtain the product;
s7, a gas chromatography determination method: heating the blank solution, the contrast solution and the sensitivity solution in a headspace bottle until the gas-liquid balance is achieved, taking the blank solution for sample injection with 1 needle, taking the sensitivity solution for sample injection with 1 needle, taking 6 parts of the contrast solution for sample injection with 1 needle respectively, carrying out temperature programming, and after the temperature programming is finished, enabling the sample to enter a detector for measurement and recording a chromatogram. Reporting the signal-to-noise ratio of 1, 2-dichloroethane in the sensitivity solution; the separation degree between the 1, 2-dichloroethane in the first needle of the control solution and the nearest adjacent peak, and the peak area, the peak area mean value and the RSD value of the 1, 2-dichloroethane of 6 samples of the control solution in each 1 needle. The results are shown in FIGS. 1 to 8 and Table 1:
the gas chromatography conditions were: the headspace sample injection bottle temperature is 60 ℃, the heat preservation time is 30min, the pressurization time is 2min, the sampling needle temperature is 70 ℃, the sample injection time is 0.2min, the cycle time is 27min, the transmission line temperature is 80 ℃, the needle pulling time is 0.4min, and the balance pressure is 15 psi. DB-624 chromatographic column, model 30m × 0.32mm × 1.8 μm, injection port temperature 170 deg.C, injection amount 1mL, split ratio 1:1, carrier gas nitrogen, flow rate 0.50mL/min, initial temperature 60 deg.C, maintaining for 2min, heating to 120 deg.C at 10 deg.C/min, heating to 220 deg.C at 30 deg.C/min, maintaining for 5min, detector temperature 250 deg.C, tail-blowing 25mL/min, and sampling frequency 20 Hz.
TABLE 1 System suitability results
Note: RS-1-RS-6 represents control solution 1-6 needles, RSD represents relative standard deviation, i.e., precision, and S/N represents signal to noise ratio.
As can be seen from FIGS. 1 to 8 and Table 1, the blank solution has no background interference to the measurement of 1, 2-dichloroethane, the signal-to-noise ratio of 1, 2-dichloroethane in the sensitive solution is 113.6 (not less than 10), the separation degree of 1, 2-dichloroethane and the nearest adjacent peak in the first needle of the control solution is 16.47 (not less than 1.5), the RSD of the peak area of 1, 2-dichloroethane entering each of 6 parts of the control solution into 1 needle is 1.84% (not more than 10.0%), and the system applicability meets the detection requirements.
Example 2 limit of quantitation test
A method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride is a quantitative limit test, which comprises the following steps:
s1, preparing a blank solution: precisely transferring 1mL of DMSO and 1mL of purified water into a 20mL headspace bottle, sealing, and shaking to obtain a blank solution.
S2, preparing a first control stock solution: taking 125mg of 1, 2-dichloroethane, putting the 1, 2-dichloroethane in a 100mL volumetric flask, diluting the 1, 2-dichloroethane to a scale with DMSO, and shaking up to obtain a first control stock solution with the 1, 2-dichloroethane concentration of 1.25 mg/mL;
s3, preparing a second control stock solution: precisely transferring 1mL of the first control stock solution into a 100mL volumetric flask, diluting the first control stock solution to a scale with DMSO, and shaking up to obtain the reagent;
s4, preparing a third contrast stock solution: precisely transferring 2mL of the second control stock solution into a50 mL volumetric flask, diluting the second control stock solution to a scale with DMSO, and shaking up to obtain the reagent;
s5, preparation of a quantitative limiting solution: the third control stock solution (1 mL) was transferred to a 10mL volumetric flask, DMSO was added to the scale, the flask was shaken well, and the solution (1 mL) and ultrapure water (1 mL) were transferred to a 20mL headspace flask, sealed and prepared into 3 parts.
S6, a gas chromatography determination method comprises the following steps: heating the blank solution and the quantitative limit solution in a headspace bottle until the gas-liquid balance is achieved, taking the blank solution for sample injection for 1 needle, taking the quantitative limit solution for continuous sample injection for 3 needles, carrying out temperature programming, and after the temperature programming is finished, allowing the sample to enter a detector for measurement and recording a chromatogram. Reporting the peak area of 1, 2-dichloroethane in the quantitative limiting solution, RSD of the peak area and signal-to-noise ratio (S/N); the concentration of the quantitative limit of 1, 2-dichloroethane and the percentage of the concentration corresponding to the concentration of the test solution were calculated. The results are shown in FIGS. 9 to 11 and Table 2:
the gas chromatography conditions were the same as in example 1.
TABLE 2 quantitative limit results
Note: RSD represents the relative standard deviation, i.e., precision, and S/N represents the signal-to-noise ratio.
As can be seen from FIGS. 9-11 and Table 2, the quantitative limiting solution was continuously injected for 3 times, and the minimum value of the peak signal-to-noise ratio of 1, 2-dichloroethane was 41.5 (not less than 10), which met the requirements; the RSD value of the peak area of the 1, 2-dichloroethane is 3.61% (less than or equal to 10.0%) after the quantitative limiting solution is continuously injected for 3 times; the concentration level of the 1, 2-dichloroethane quantitative limit solution is 0.025 mu g/mL, the limit is 0.50ppm, and the method quantitative limit meets the detection requirement.
Example 3 specificity test
A method specificity test for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride comprises the following steps:
s1, preparing a blank solution: precisely transferring 1mL of DMSO and 1mL of purified water into a 20mL headspace bottle, sealing, and shaking to obtain a blank solution.
S2, preparing a first control stock solution: taking 125mg of 1, 2-dichloroethane, putting the 1, 2-dichloroethane in a 100mL volumetric flask, diluting the 1, 2-dichloroethane to a scale with DMSO, and shaking up to obtain a first control stock solution with the 1, 2-dichloroethane concentration of 1.25 mg/mL;
s3, preparing a second control stock solution: precisely transferring 1mL of the first control stock solution into a 100mL volumetric flask, diluting the first control stock solution to a scale with DMSO, and shaking up to obtain the reagent;
s4, preparing a third contrast stock solution: precisely transferring 2mL of the second control stock solution into a50 mL volumetric flask, diluting the second control stock solution to a scale with DMSO, and shaking up to obtain the reagent;
s4, preparing a contrast solution: precisely transferring 1mL of the third control stock solution into a 20mL headspace bottle, precisely adding 1mL of purified water, and sealing to obtain the final product.
S5, preparation of a test solution: precisely weighing 100mg of a sample to be tested in a 20mL headspace bottle, adding 1mL of LDMSO for dissolving, adding 1mL of ultrapure water, sealing, and shaking uniformly to obtain the final product;
s6.100% preparation of sample solution for adding standard: precisely weighing 100mg of a sample to be tested in a 20mL headspace bottle, adding 1mL of third control stock solution, dissolving, adding 1mL of ultrapure water, sealing, shaking uniformly, and preparing 1 part of 100% sample standard solution;
s7, preparation of a peak attribution solution: respectively transferring 1mL of LDMSO and 1mL of ultrapure water into 11 headspace bottles, sequentially adding a proper amount of methanol, ethanol, ethyl acetate, dichloromethane, toluene, N-Dimethylformamide (DMF) and N, N-dimethylpyrrolidone (NMP), sealing, and shaking uniformly to obtain the final product.
S8, a gas chromatography determination method: and heating the blank solution, the sample solution, the reference solution, the 100% sample adding standard solution and the peak belonging solution in a headspace bottle until the gas-liquid balance is achieved, then respectively injecting 2 samples into the blank solution, the sample solution, the reference solution and the 100% sample adding standard solution, respectively injecting 1 sample into each peak belonging solution, carrying out temperature programming, and after the temperature programming is finished, allowing the sample to enter a detector for measurement and recording a corresponding chromatogram. Reporting the retention time, the peak area and the separation degree of adjacent peaks of the 1, 2-dichloroethane in the blank solution, the test solution, the reference solution and the test solution added standard solution, and the retention time of each solvent to be detected in the solution to which each peak belongs. The results are shown in fig. 1, fig. 12 to fig. 24, and table 3:
the gas chromatography conditions were the same as in example 1.
TABLE 3 specificity results
Note: N/A represents that the peak of 1, 2-dichloroethane is not shown.
It can be seen from fig. 1, fig. 12 to fig. 24 and table 3 that 1, 2-dichloroethane does not interfere in the blank solution and the test solution; the minimum value of the separation degree of the 1, 2-dichloroethane and the adjacent chromatographic peak in the test solution, the reference solution and the test sample and standard solution is 13.93 (more than or equal to 1.5), and the requirements of pharmacopoeia are met; the retention time of the 1, 2-dichloroethane in the test solution or the test sample added standard solution is consistent with that of the control solution; compared with the sample solution, the peak area of the 1, 2-dichloroethane in the sample added standard solution is increased; the method has good specificity and is suitable for detecting the residual 1, 2-dichloroethane.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A method for detecting 1, 2-dichloroethane solvent residue in sultopride hydrochloride is characterized by comprising the following steps:
(1) preparing a blank solution, a control solution and a test solution;
(2) pretreating the blank solution, the reference solution and the sample solution by adopting a headspace sampler, heating until the gas-liquid balance is achieved, injecting gas above a headspace bottle into a gas chromatograph, and analyzing the sultopride hydrochloride by using the gas chromatography to obtain a chromatogram so as to determine the content of the 1, 2-dichloroethane.
2. The method of claim 1, wherein the blank solution is prepared by: and (3) uniformly mixing the DMSO with the same volume with the purified water to obtain a blank solution.
3. The method of claim 1, wherein the control solution is prepared by: adding DMSO into 1, 2-dichloroethane to dilute to obtain a first control stock solution with 1, 2-dichloroethane concentration of 1.25 mg/mL; adding DMSO into the first control stock solution to dilute 2500 times to obtain a second control stock solution; adding purified water with the same volume as the second control stock solution, and mixing to obtain the control solution.
4. The method of claim 1, wherein the sample solution is prepared by: adding DMSO into a test sample to dissolve, adding purified water with the same volume as the DMSO, and mixing uniformly to obtain a test sample solution; the dosage ratio of the test sample to DMSO is 100 mg: 1 mL.
5. The method of claim 1, wherein the gas chromatography conditions are:
headspace injector conditions: the headspace sample injection bottle temperature is 60-65 ℃, the heat preservation time is 25-30 min, the pressurization time is 1.8-2.2 min, the sampling needle temperature is 70-75 ℃, the sample injection time is 0.2-0.3 min, the cycle time is 27-30 min, and the transmission line temperature is 80-85 ℃;
the temperature of a sample inlet is 170-175 ℃, the sample injection amount is 1.0-1.2 mL, and the split ratio is 1: 1-2: 1;
the carrier gas is nitrogen, and the flow rate is 0.45-0.50 mL/min;
temperature programming: the initial temperature is 58-60 ℃, the temperature is increased to 115-120 ℃ at the speed of 9-11 ℃/min after the initial temperature is maintained for 2-3 min, the temperature is increased to 210-220 ℃ at the speed of 28-30 ℃/min, and the initial temperature is maintained for 5-6 min;
a detector: a μ ECD detector;
the temperature of the detector is 250-265 ℃, the tail blowing is 25-30 mL/min, and the sampling frequency is 20-50 Hz;
the chromatographic column is a DB-624 chromatographic column with the model of 30m multiplied by 0.32mm multiplied by 1.8 mu m.
6. The method of claim 5, wherein the headspace injector conditions are: the headspace sample injection bottle temperature is 60 ℃, the heat preservation time is 30min, the pressurization time is 2min, the sampling needle temperature is 70 ℃, the sample injection time is 0.2min, the cycle time is 27min, the transmission line temperature is 80 ℃, the needle pulling time is 0.4-0.5 min, and the balance pressure is 12-15 psi.
7. The method according to claim 5, wherein the injection port temperature is 170 ℃ and the split ratio is 1: 1.
8. The method of claim 5, wherein the carrier gas flow rate is 0.50 mL/min.
9. The method of claim 5, wherein the programmed temperature: the initial temperature is 60 ℃, the temperature is maintained for 2min, then the temperature is increased to 120 ℃ at the speed of 10 ℃/min, and then the temperature is increased to 220 ℃ at the speed of 30 ℃/min, and the temperature is maintained for 5 min.
10. The method of claim 5, wherein the detector temperature is 250 ℃ and the tail gas is blown at 25 mL/min.
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| CN112964813A (en) * | 2019-12-13 | 2021-06-15 | 金陵药业股份有限公司 | Method for measuring residual quantity of organic solvent in fasudil hydrochloride |
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| CN112964813A (en) * | 2019-12-13 | 2021-06-15 | 金陵药业股份有限公司 | Method for measuring residual quantity of organic solvent in fasudil hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| 张惠 等: "两种GC法测定胶粘剂中卤代烃的方法比较研究", 广州化工, vol. 40, no. 20, pages 91 - 93 * |
| 白秀萍 等: "GC测定氢化可的松中甲醇、氯仿、1, 2-二氯乙烷的残留量", 食品与药品, vol. 21, no. 2, pages 152 - 156 * |
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