阅读说明：本技术 一种蔗糖八硫酸酯钾中多种残留溶剂的气相检测方法 (Gas phase detection method for various residual solvents in sucrose octasulfate potassium ) 是由 甘莉 吴峥 王秋贺 颜蓉 王飞飞 于 2021-09-10 设计创作，主要内容包括：本发明涉及一种蔗糖八硫酸酯钾中多种残留溶剂的气相检测方法,所述蔗糖八硫酸酯钾中含有多种残留溶剂,所述方法具体包括以下步骤：(a)制备空白溶液、含残留溶剂的对照品溶液和供试品溶液,所述供试品为蔗糖八硫酸酯钾；(b)采用顶空进样气相色谱法,分别检测空白溶液、对照品溶液及供试品溶液,记录相应的图谱,按外标法利用峰面积计算供试品中残留溶剂的残留量。与现有技术相比,本发明能够准确、迅速地检测蔗糖八硫酸酯钾中残留的甲醇、乙腈、醋酸异丙酯、吡啶和2-甲基吡啶的含量,且具有灵敏度高、重现性良好等优点。(The invention relates to a gas phase detection method for multiple residual solvents in sucrose potassium octasulfate, which contains multiple residual solvents and specifically comprises the following steps: (a) preparing a blank solution, a reference substance solution containing a residual solvent and a test sample solution, wherein the test sample is sucrose octasulfate potassium; (b) respectively detecting the blank solution, the reference solution and the test solution by adopting a headspace sample injection gas chromatography, recording corresponding spectrums, and calculating the residual quantity of the residual solvent in the test solution by utilizing peak area according to an external standard method. Compared with the prior art, the method can accurately and rapidly detect the content of residual methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine in the sucrose octasulfate potassium, and has the advantages of high sensitivity, good reproducibility and the like.)

1. A gas phase detection method for multiple residual solvents in sucrose potassium octasulfate is characterized in that the sucrose potassium octasulfate contains multiple residual solvents, and the method specifically comprises the following steps:

(a) preparing a blank solution, a reference substance solution containing a residual solvent and a test sample solution, wherein the test sample is sucrose octasulfate potassium;

(b) respectively detecting a blank solution, a reference solution and a sample solution by adopting a headspace sample injection gas chromatography, recording corresponding spectrums, and calculating the residual quantity of the residual solvent in the sample by utilizing peak area according to an external standard method, wherein the calculation formula is shown as (I):

wherein: ax is the peak area of the corresponding component peak in the test solution;

ar is the peak area of the corresponding component peak in the reference solution;

cr-concentration of the corresponding component in the control solution (mg/mL);

cx-concentration of sample in sample solution (mg/mL).

2. The method according to claim 1, wherein in the step (a), the blank solution is a mixed solvent of DMSO and water, wherein the mixed solvent is prepared according to the volume ratio of DMSO to water to 1: 9.

3. The method according to claim 1, wherein in the step (a), the solvent is a mixed solvent of DMSO and water prepared according to a volume ratio of DMSO to water of 1:9, and the solute is the residual solvent.

4. The method of claim 1, wherein the residual solvents comprise methanol, acetonitrile, isopropyl acetate, pyridine, and 2-methylpyridine,

in the step (a), when the residual solvent is methanol, the concentration of the reference substance solution is 0.3 mg/mL;

when the residual solvent is acetonitrile, the concentration of the control solution is 0.041 mg/mL;

when the residual solvent is isopropyl acetate, the concentration of the control solution is 0.5 mg/mL;

when the residual solvent is pyridine solution, the concentration of the reference substance solution is 0.02 mg/mL;

when the residual solvent is 2-methylpyridine solution, the concentration of the control solution is 0.02 mg/mL.

5. The method according to claim 1, wherein in the step (a), the solvent is a mixed solvent of DMSO and water prepared according to a volume ratio of DMSO to water of 1:9, and the solute is sucrose octasulfate potassium.

6. The method of claim 1, wherein the concentration of the potassium sucrose octasulfate in the sample solution is 100 mg/mL.

7. The method of claim 1, wherein in step (b), the gas chromatography conditions are as follows:

temperature of the column: the initial temperature is 90-110 ℃, the temperature is maintained for 15-25 min, the temperature is increased to 190-210 ℃ at the speed of 15-25 ℃/min, and the temperature is maintained for 4-6 min;

sample inlet temperature: 190-210 ℃;

carrier gas: high-purity nitrogen with the flow rate of 1.8-2.2mL/min and the carrier gas split ratio of (9-11) to 1;

a detector: a hydrogen flame ionization detector, wherein the temperature is 245-255 ℃;

headspace conditions: the heating temperature of the headspace bottle is 75-95 ℃, the quantitative ring is 80-100 ℃, the transmission line is 85-105 ℃, the heating time of the headspace bottle is 20-40 min, and the pressurization is 0.05-0.11 min.

8. The method of claim 7, wherein the gas chromatography conditions in step (b) are as follows:

temperature of the column: starting temperature at 100 deg.C, maintaining for 20min, increasing to 200 deg.C at 20 deg.C/min, and maintaining for 5 min;

sample inlet temperature: 200 ℃;

carrier gas: high-purity nitrogen with the flow rate of 2.0mL/min and the carrier gas split ratio of 10: 1;

a detector: a hydrogen flame ionization detector with the temperature of 250 ℃;

headspace conditions: heating the headspace bottle at 85 deg.C, transferring line at 90 deg.C, transferring line at 95 deg.C, heating the headspace bottle for 30min, and pressurizing for 0.08 min.

9. The method of claim 1, wherein the chromatographic column used in step (b) is Agilent DB-6246% cyanopropylmethylpolysiloxane capillary chromatographic column.

10. The method of claim 1, wherein the residual solvents in the potassium sucrose octasulfate comprise methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine, the content of methanol is not more than 0.3 wt%, the content of acetonitrile is not more than 0.041 wt%, the content of isopropyl acetate is not more than 0.5 wt%, the content of pyridine is not more than 0.02 wt%, and the content of 2-methylpyridine is not more than 0.02 wt%.

Technical Field

The invention belongs to the field of drug analysis and detection, and particularly relates to a gas phase detection method for various residual solvents in sucrose octasulfate potassium.

Background

Sucrose octasulfate is used as gastric mucosa protectant for treating gastric ulcer and duodenitis. With the advent of irinotecan liposome drug Onvyde in the United states, sucrose octasulfate has attracted attention in the pharmaceutical community as a novel pharmaceutical adjuvant.

The raw material medicine, the auxiliary material and the preparation can select proper organic solvent to improve the yield or determine the medicine property in the production process, but the organic solvent can not be completely removed in the preparation process. When the amount of residual solvent contained in the drug is higher than a safe value, the drug is harmful to the human body, and thus, it is necessary to pay special attention to the control of the amount of residual solvent.

Disclosure of Invention

The invention aims to provide a gas phase detection method for various residual solvents in sucrose octasulfate potassium.

The purpose of the invention is realized by the following technical scheme:

a gas phase detection method for multiple residual solvents in sucrose potassium octasulfate, wherein the sucrose potassium octasulfate contains multiple residual solvents, and the method specifically comprises the following steps:

(a) preparing a blank solution, a reference substance solution containing a residual solvent and a test sample solution, wherein the test sample is sucrose octasulfate potassium;

(b) respectively detecting a blank solution, a reference solution and a sample solution by adopting a headspace sample injection gas chromatography, recording corresponding spectrums, and calculating the residual quantity of the residual solvent in the sample by utilizing peak area according to an external standard method, wherein the calculation formula is shown as (I):

wherein: ax is the peak area of the corresponding component peak in the test solution;

ar is the peak area of the corresponding component peak in the reference solution;

cr-concentration of the corresponding component in the control solution (mg/mL);

cx — concentration of sample in sample solution (mg/mL), i.e. the concentration of potassium sucrose octasulfate that is weighed out, which may contain residual solvent. The amount of residual solvent refers to the mass percentage of a certain residual solvent in the total amount of the sample (wherein,the concentration of a certain residual solvent in the test solution is obtained, then the concentration of the test solution is divided by the concentration of the test solution in the test solution and multiplied by the percentage to obtain the content percentage of the residual solvent in the test solution, and the core of the calculation formula is that the peak areas with different concentrations are different). When the content of the sample is detected, a linear regression equation is not used (a linear test is used for determining the detection range of the method), and a single-point external standard method is used.

In the step (a), the blank solution is a mixed solvent of DMSO and water prepared in a volume of DMSO: water of 1: 9.

In the step (a), the solvent in the control solution is a mixed solvent of DMSO and water prepared in a volume ratio of DMSO to water of 1:9, and the solute is a residual solvent.

The residual solvent includes methanol, acetonitrile, isopropyl acetate, pyridine, and 2-methylpyridine.

In the step (a), when the residual solvent is methanol, the concentration of the reference substance solution is 0.3 mg/mL;

when the residual solvent is acetonitrile, the concentration of the control solution is 0.041 mg/mL;

when the residual solvent is isopropyl acetate, the concentration of the control solution is 0.5 mg/mL;

when the residual solvent is pyridine solution, the concentration of the reference substance solution is 0.02 mg/mL;

when the residual solvent is 2-methylpyridine solution, the concentration of the control solution is 0.02 mg/mL. These concentration values are based on the respective concentrations of the residual solvent control calculated from the values "test sample potassium sucrose octasulfate, the residual solvent includes methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine, the content of methanol is not more than 0.3 wt%, the content of acetonitrile is not more than 0.041 wt%, the content of isopropyl acetate is not more than 0.5 wt%, the content of pyridine is not more than 0.02 wt%, the content of 2-methylpyridine is not more than 0.02 wt%, and the concentration of potassium sucrose octasulfate is 100 mg/mL". The concentration here is a concentration of a single residual solvent as a solute, and if the solute is a mixture of a plurality of residual solvents, the concentrations may be prepared in a one-to-one correspondence.

In the step (a), in the sample solution, a solvent is a mixed solvent of DMSO and water prepared according to the volume ratio of DMSO to water to 1:9, and a solute is sucrose octasulfate potassium;

the concentration of the potassium sucrose octasulfate in the test solution was 100mg/mL (this concentration is the concentration of the weighed potassium sucrose octasulfate which may contain residual solvent). Because the detection limit of pyridine in the residual solvent is low, the concentration of the sample needs to be increased, the concentration of 100mg/mL accords with the solubility of the sucrose potassium octasulfate sample, and if the concentration is increased, the sucrose potassium octasulfate sample cannot be completely dissolved.

In step (b), the gas chromatography conditions were as follows:

temperature of the column: the initial temperature is 90-110 ℃, the temperature is maintained for 15-25 min, the temperature is increased to 190-210 ℃ at the speed of 15-25 ℃/min, and the temperature is maintained for 4-6 min;

sample inlet temperature: 190-210 ℃;

carrier gas: high-purity nitrogen with the flow rate of 1.8-2.2mL/min and the carrier gas split ratio of (9-11) to 1;

a detector: a hydrogen flame ionization detector, wherein the temperature is 245-255 ℃;

headspace conditions: the heating temperature of the headspace bottle is 75-95 ℃, the quantitative ring is 80-100 ℃, the transmission line is 85-105 ℃, the heating time of the headspace bottle is 20-40 min, and the pressurization is 0.05-0.11 min.

Preferably, in step (b), the gas chromatography conditions are as follows:

temperature of the column: starting temperature at 100 deg.C, maintaining for 20min, increasing to 200 deg.C at 20 deg.C/min, and maintaining for 5 min;

sample inlet temperature: 190-210 ℃, and more preferably 200 ℃;

carrier gas: high-purity nitrogen with the flow rate of 1.8-2.2mL/min, more preferably 2.0mL/min and the carrier gas split ratio of 10: 1;

a detector: a hydrogen flame ionization detector (FID detector for short) with the temperature of 245-255 ℃, and further preferably 250 ℃;

headspace conditions: heating the headspace bottle at 85 deg.C, transferring line at 90 deg.C, transferring line at 95 deg.C, heating the headspace bottle for 30min, and pressurizing for 0.08 min.

In step (b), the chromatographic column used was an Agilent DB-6246% cyanopropylmethylpolysiloxane capillary chromatographic column.

In the potassium sucrose octasulfate, the residual solvent comprises methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine, the content of the methanol is not more than 0.3 wt%, the content of the acetonitrile is not more than 0.041 wt%, the content of the isopropyl acetate is not more than 0.5 wt%, the content of the pyridine is not more than 0.02 wt%, and the content of the 2-methylpyridine is not more than 0.02 wt% (the limits are determined according to the limit standard of the residual solvent commonly found in the medicines in the fourth 0861 residual solvent assay of Chinese pharmacopoeia).

The invention aims at 5 organic solvent residues of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine introduced by a synthesis process in the sucrose octasulfate potassium, and utilizes a headspace sample injection gas chromatography (headspace sample injection, namely gas is used as a solvent to extract volatile components in a sample, so that the five residual solvents in the sample can be extracted in the headspace sample injection certainly as long as the five residual solvents exist in the sample), thereby reducing the influence of a sample matrix and finally realizing the separation and detection of the 5 residual solvents.

The invention has the following beneficial effects:

1. the gas chromatography condition can simultaneously detect the content of 5 residual solvents of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine in the sucrose octasulfate potassium;

2. the detection method provided by the invention is simple and convenient to operate, and meanwhile, methodology verification is carried out on the established detection method, so that the method is proved to be high in accuracy, high in sensitivity, strong in specificity and good in reproducibility. The safety of the auxiliary materials can be ensured by controlling the content of the residual solvent in the auxiliary materials, and the safety of the preparation is further ensured.

Drawings

FIG. 1 is a gas chromatogram of a blank solution;

FIG. 2 is a gas chromatogram of a mixed control solution of methanol, acetonitrile, isopropyl acetate, pyridine, and 2-methylpyridine;

FIG. 3 is a gas chromatogram of the detection limit;

FIG. 4 is a gas chromatogram of a limit of quantitation test;

FIG. 5 is a gas chromatogram of EB 210520;

FIG. 6 is a gas chromatogram of EB 210228;

fig. 7 is a gas chromatogram of EB 201218.

Detailed Description

The invention is described in detail below with reference to the figures and specific embodiments.

The invention discloses a gas phase detection method for residual solvent in sucrose octasulfate potassium, and a person skilled in the art can modify detection conditions appropriately by referring to the content of the invention.

The reagent or instrument used in the gas phase detection method of residual solvent in sucrose octasulfate potassium provided by the invention can be purchased from the market.

The invention will be further elucidated with reference to the following examples:

examples

1. Instrument and reagent

The instrument comprises the following steps: agilent6890 gas chromatograph, Agilent G1888 headspace sampler, analytical balance

Reagent testing: all the reagents are pure in chromatography, and the test sample of the sucrose octasulfate potassium is purchased from ai Wei Tuo (Shanghai) pharmaceutical technology Co.

2. Chromatographic conditions

A chromatographic column: agilent DB-624(30 m.times.0.53 mm. times.3 μm);

temperature of the column: starting temperature at 100 deg.C, maintaining for 20min, increasing to 200 deg.C at 20 deg.C/min, and maintaining for 5 min;

sample inlet temperature: 200 ℃;

carrier gas: high-purity nitrogen with the flow rate of 2.0mL/min and the split ratio of 10: 1;

a detector: a hydrogen flame ionization detector with the temperature of 250 ℃;

headspace conditions: heating the headspace bottle at 85 deg.C, transferring line at 90 deg.C, transferring line at 95 deg.C, heating the headspace bottle for 30min, and pressurizing for 0.08 min.

Other parameters: the hydrogen flow rate is 30mL/min, the air flow rate is 400mL/min, and the tail blowing rate is 25 mL/min.

3. Solution preparation

Blank solution: a mixed solvent of DMSO and water was prepared in a volume of DMSO: water 1:9, and then 1.0mL was put into a headspace bottle and sealed to prepare a blank solution.

Control solution: an appropriate amount of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine is precisely weighed into a measuring flask, and a mixed solution of DMSO and water (volume ratio DMSO: water ═ 1:9) is added to quantitatively dilute the mixture into a mixed solution containing 0.3mg, 0.041mg, 0.5mg, 0.02mg and 0.02mg of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine in each 1mL (namely, the mixed solution contains five solvents of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine at the same time). Precisely transferring 1.0mL of the mixed solution, placing in a headspace bottle, and sealing to obtain a control solution.

Test solution: precisely weighing 100mg of sucrose octasulfate potassium, placing the sucrose octasulfate potassium in a 20mL headspace bottle, adding a solvent DMSO and 1.0mL of water (1:9), shaking to dissolve, sealing, and shaking uniformly to obtain a sample solution.

4. Determination of content

Injecting the blank solution, the reference solution and the sample solution into a gas chromatograph by adopting a headspace sampling method, recording a chromatogram, and calculating the content of each residual solvent by peak area according to an external standard method. In the invention, the sucrose octasulfate potassium contains methanol not more than 0.3%, acetonitrile not more than 0.041%, isopropyl acetate not more than 0.5%, and pyridine and 2-methylpyridine not more than 0.02%.

The calculation formula is as follows:

wherein: ax is the peak area of the corresponding component peak in the test solution;

ar is the peak area of the corresponding component peak in the reference solution;

cr-concentration of the corresponding component in the control solution (mg/mL);

cx-concentration of sample in sample solution (mg/mL).

5. Test results

The test results are shown in FIGS. 1 to 7.

The test result shows that the blank solution has no interference to the test solution and the reference solution, the separation degree of 5 solvent peaks in the reference solution is good, and the sample detection result meets the standard.

Test example 1 System suitability test

Precisely measuring a blank solution, a peak positioning solution of methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine and a mixed reference solution (namely the reference solution prepared in the step 3) by 1.0mL respectively, and putting 7 solutions in different headspace bottles, sealing and injecting samples respectively. The retention times and degrees of separation of the components are shown in Table 1 (separation was performed using the mixed control solution, and the peak positions of the other 5 pooled solutions were determined for each solvent), the gas chromatogram of the blank solution is shown in FIG. 1, and the gas chromatogram of the mixed control solution is shown in FIG. 2 (wherein the peak at 4.730 corresponds to methanol, the peak at 5.717 corresponds to acetonitrile, the peak at 7.830 corresponds to isopropyl acetate, the peak at 11.822 corresponds to pyridine, and the peak at 15.687 corresponds to 2-methylpyridine, as shown in detail in FIG. 2). The result shows that the blank solution does not interfere with residual solvents, all components are completely separated, the separation degree R is greater than 1.5, and the peak symmetry is good.

TABLE 1 retention time and degree of separation of the components

Test example 2 Linear test

Preparation of a linear solution (the linear solution contains five solvents at the same time): the concentration of the linear solution ranges from the quantitative limit of residual solvent to 150% of the control solution concentration, respectively: limits of quantitation (10%), 50%, 80%, 100%, and 150% five concentration levels (in mg/mL). Respectively transferring 1.0mL of each linear solution, placing the linear solution in a 20mL headspace bottle, injecting the linear solution into a gas chromatograph by adopting a headspace sampling method, recording a chromatogram, and calculating a linear regression equation by taking the solution concentration as a horizontal coordinate and taking a peak area value as a vertical coordinate. The results are shown in Table 2 and show the linear regression coefficient R of 5 residual solvents²The linear relation is good within 0.990-1.000.

TABLE 2 measurement of the Linear relationship

Wherein y represents the area of the peak corresponding to each component, and x represents the concentration (in mg/mL) of each component.

Test example 3 precision test

Preparing a mixed control solution (namely the control solution prepared in the step 3), sucking 1.0-20 mL of headspace bottles, sealing, and taking 6 samples in parallel. And (3) continuously introducing the sample in the headspace for 6 times, recording peak areas of all components in the sample introduction for 6 times, and calculating relative standard deviation, wherein the result is shown in a table 3. The results show that the relative standard deviation of the peak areas of the 5 residual solvents is not more than 10.0 percent, and the precision of the chromatographic system is good.

TABLE 3 precision test results

Test example 4 recovery test

According to the Chinese pharmacopoeia 9101, the accuracy refers to the degree of closeness of the result measured by the method to the true value or the reference value, and is generally expressed by the recovery rate (%). The accuracy should be determined within the specified range.

100mg of a sample of sucrose octasulfate potassium (Avena, Shanghai, pharmaceutical science and technology Co., Ltd., batch No.: EB201218) was precisely weighed into a 20mL headspace bottle, and dissolved in 1.0mL of DMSO-water (1:9) to prepare a blank solution. In addition, 9 parts of the same test sample of sucrose octasulfate potassium salt, 100mg of each part, and 3 parts of each part are precisely weighed, and 1.0mL of linear solutions with the concentration respectively being 10% of the quantitative limit of the residual solvent, 100% of the concentration of the reference solution and 150% of the concentration of the reference solution are respectively transferred and dissolved in each group. The results of the sequential measurements, and the recovery rate was calculated as follows, and are shown in Table 5. The experimental result shows that the recovery rates of the five solvents are all 80-120%, and the RSD values are all less than or equal to 10.0%, which indicates that the method has good accuracy.

Recovery ═ percent (normalized sample measurement value-sample measurement value) ÷ normalized amount × 100%

Wherein the measured value of the labeled sample is the content of each residual solvent in the labeled sample, and the measured value of the sample is the content of the residual solvent in the unlabeled sample.

All the test values of the test pieces are 0; the values measured for the spiked samples are given in Table 4 below:

TABLE 4

TABLE 5 recovery test results

(in the guiding principle of the pharmacopoeia 9101, the recovery rate limit is 90-108% under the condition that the content of the component to be detected is 0.1%, but the limit can be properly relaxed in the actual detection)

Test example 5 detection and quantitation limits

The signal-to-noise ratio S/N is 10 as the limit of quantitation, the signal-to-noise ratio S/N is 3 as the limit of detection, and the mixed control solution at the limit of quantitation is diluted 3 times with the diluent DMSO: water (1:9) as the limit of detection test solution. 1mL of the sample is injected into a headspace bottle, and a chromatogram (detailed in figures 3 and 4) is recorded to calculate the detection limit and the quantification limit, and the result is shown in Table 6.

TABLE 6 detection limit and quantitation limit results

Test example 6 stability examination

Precisely weighing 100mg to 20mL of sucrose octasulfate test sample in a headspace bottle, adding DMSO: 1.0mL of water (1:9), sealing, standing at room temperature for 0, 2, 4 and 6 hours, and sequentially detecting, wherein 5 residual solvents are not detected. The result shows that the method is suitable for measuring the residual solvent in the sucrose octasulfate, and the data is reliable.

Test example 7 durability tester temperature Change test

The headspace detector temperature was varied to 245 ℃ and 255 ℃ and other chromatographic conditions were kept constant, and a single injection of the mixed control solution was injected under each condition. The test results are compared with the results obtained at the temperature of 250 ℃ of the original detector, the results are shown in Table 7, the results show that the separation effect can meet the requirements when the results are measured according to the chromatographic conditions, and the temperature change of the detector within the range of 245-255 ℃ has no influence on the separation of the residual solvent in the sucrose octasulfate potassium.

TABLE 7 temperature variation result comparison table of durability detector

Test example 8 durability Carrier gas flow Rate Change test

The nitrogen flow rate was varied to 1.8mL/min and 2.2mL/min, the other chromatographic conditions were kept constant, and a single injection of the mixed control solution was injected under each condition. The test result is compared with the result obtained under the original carrier gas flow rate of 2.0mL/min, and the result is shown in Table 8, and the result shows that the separation effect can meet the requirement determined according to the chromatographic conditions, and the change of the carrier gas flow rate within the range of 1.8-2.2mL/min has no influence on the separation of the residual solvent in the sucrose octasulfate potassium.

TABLE 8 comparison table of variation results of the flow rate of the durable carrier gas

Test example 9 durability sample inlet temperature Change test

Changing the temperature of the injection port to 190 ℃ and 210 ℃, keeping other chromatographic conditions unchanged, and injecting a needle of the mixed reference substance solution under each condition. The test result is compared with the result at the original injection port temperature of 200 ℃, the result is shown in table 9, the result shows that the separation effect can meet the requirement when the test is carried out under the chromatographic conditions, and the change of the injection port temperature within the range of 190-210 ℃ has no influence on the separation of the residual solvent in the sucrose octasulfate potassium.

TABLE 9 comparison table of temperature variation results of durable sample inlet

Test example 10 sample testing

3 batches of the test solution of sucrose octasulfate potassium are prepared according to the method for preparing the test solution shown in the step 3 (the obtained test solution is clear and transparent, and the situation that the residual solvent is not dissolved is avoided), the measurement results are shown in table 10 according to the chromatographic method disclosed by the invention, and the gas chromatographic results are respectively shown in fig. 5-7 (wherein, an EB210520 gas chromatogram is shown in fig. 5, an EB210228 gas chromatogram is shown in fig. 6, and an EB201218 gas chromatogram is shown in fig. 7, the samples are all purchased from Aiwei medicine science and technology Limited company, the labels are sample numbers which are self-provided by the Aiwei medicine science and technology Limited company, and in addition, the three batches of samples have been subjected to nuclear magnetic detection and have high purity and no residual solvent), and 5 residual solvents are not detected in the three batches of samples.

TABLE 10 determination of residual solvent in three samples of sucrose octasulfate Potassium

The method of the invention is verified by methodology, the reliability of the method is proved, and the accuracy of the method is also proved in a recovery rate test. In addition, because the invention adopts headspace sampling, when any one or more of the five solvents exist in a sample, the sample is detected without fail, and other possibilities of undetected detection are eliminated.

In conclusion, the method for detecting the content of 5 residual solvents, namely methanol, acetonitrile, isopropyl acetate, pyridine and 2-methylpyridine in the sucrose octasulfate potassium has the advantages of high sensitivity, high accuracy and good repeatability, and can effectively control the quality of the product. In addition, the invention adopts the mixed solvent of water and organic solvent as the solvent, can effectively improve the release of residual organic solvent in the sample, improve the sensitivity of the method, and simultaneously, the use of organic solvent can be reduced by using a large proportion of water as the solvent, thereby reducing the damage to the environment and experimenters in the analysis and detection process.

It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.

The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.