CN116465985A - Method for detecting residual solvent in alpha-ribose mesylate by gas chromatography - Google Patents

Method for detecting residual solvent in alpha-ribose mesylate by gas chromatography Download PDF

Info

Publication number
CN116465985A
CN116465985A CN202310195703.3A CN202310195703A CN116465985A CN 116465985 A CN116465985 A CN 116465985A CN 202310195703 A CN202310195703 A CN 202310195703A CN 116465985 A CN116465985 A CN 116465985A
Authority
CN
China
Prior art keywords
temperature
gas chromatography
residual solvent
ribose
mesylate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202310195703.3A
Other languages
Chinese (zh)
Other versions
CN116465985B (en
Inventor
白玮丽
林欣怡
韩瑶瑶
刘梦婷
唐婷婷
周军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jari Pharmaceutical Co ltd
Original Assignee
Jari Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jari Pharmaceutical Co ltd filed Critical Jari Pharmaceutical Co ltd
Priority to CN202310195703.3A priority Critical patent/CN116465985B/en
Publication of CN116465985A publication Critical patent/CN116465985A/en
Application granted granted Critical
Publication of CN116465985B publication Critical patent/CN116465985B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/86Signal analysis
    • G01N30/8675Evaluation, i.e. decoding of the signal into analytical information
    • G01N30/8679Target compound analysis, i.e. whereby a limited number of peaks is analysed
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Library & Information Science (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

The invention discloses a method for detecting residual solvent in alpha-ribose mesylate by using gas chromatography, which belongs to the technical field of chemical detection, wherein the residual solvent in the alpha-ribose mesylate is detected by using the gas chromatography, the instrument is a gas chromatograph, the detector is a FID detector, a chromatographic column adopts a DB-WAX quartz capillary chromatographic column, and carrier gas is N 2 The flow rate is 3.0mL/min, the split ratio is 20:1, and the column temperature is as follows: maintaining at 40deg.C for 10 min, heating to 80deg.C at 10deg.C per minute, heating to 250deg.C per minute for 3 min, introducing sample into the headspace, balancing temperature at 90deg.C, quantifying ring temperature at 100deg.C, and transmitting line temperature at 110deg.C for 30min; sample injection volume: 1.0ml, can effectively separate the residual solvent in the alpha-ribose mesylate and quantitatively detect the content of the residual solvent, and the method has the advantages of simple operation, strong specificity, high sensitivity, high accuracy, good linearity and durability, and can accurately and rapidly determine the alpha-room ratioResidual amount of 8 solvents in ribomethane sulfonate.

Description

一种气相色谱法检测α-核糖甲磺酸酯中残留溶剂的方法A method for detecting residual solvent in α-ribose mesylate by gas chromatography

技术领域technical field

本发明属于化学检测技术领域,特别涉及一种气相色谱法检测α-核糖甲磺酸酯中残留溶剂的方法。The invention belongs to the technical field of chemical detection, in particular to a method for detecting residual solvent in α-ribose mesylate by gas chromatography.

背景技术Background technique

α-核糖甲磺酸酯是盐酸吉西他滨原料药合成中重要的起始物料,盐酸吉西他滨是一种临床应用广泛的抗癌药,其注射剂在许多国家上市,在源头控制好起始物料的质量尤为重要,目前对于α-核糖甲磺酸酯中残留溶剂的检测方法还没有报道,α-核糖甲磺酸酯中有机溶剂残留对产品质量有一定的影响,因此,开发出一种能有效检测α-核糖甲磺酸酯中残留溶剂的检测方法是十分必要的,我们经过长时间研究终于研究出一种能检测出α-核糖甲磺酸酯中残留溶剂的方法,而且此方法操作方便,检测效果较佳。α-Ribose mesylate is an important starting material in the synthesis of gemcitabine hydrochloride raw materials. Gemcitabine hydrochloride is an anticancer drug widely used in clinical practice. Its injections are listed in many countries. It is particularly important to control the quality of starting materials at the source. At present, there is no report on the detection method of residual solvents in α-ribose mesylate. Residual organic solvents in α-ribose mesylate have a certain impact on product quality. Yes, after a long period of research, we have finally developed a method that can detect residual solvents in α-ribose mesylate, and this method is easy to operate and has better detection results.

发明内容Contents of the invention

针对现有技术的不足,本发明的目的在于提供一种气相色谱法检测α-核糖甲磺酸酯中残留溶剂的方法,包括以下步骤:For the deficiencies in the prior art, the object of the present invention is to provide a method for gas chromatography detection of residual solvent in α-ribose mesylate, comprising the following steps:

1)仪器与色谱条件的选择:气相色谱仪;色谱柱为DB-WAX(30m×0.53mm×1.0μm)毛细管色谱柱;采用FID检测器,色谱柱初始温度为35-45℃,保持时间为8-12min,然后以8-12℃/min的升温速率升至80℃,再以35-45℃/min的升温速率升至色谱柱最终温度为250℃,色谱柱最终温度保持时间为2-5min;载气为氮气,所述载气流速为2.5-3.5ml/min,分流比为20:1;进样口温度为190-210℃,检测器温度为240-260℃;进样方式为顶空进样,平衡温度90℃,定量环温度100℃,传输线温度110℃,平衡时间30min;进样体积为1.0mL。1) Selection of instrument and chromatographic conditions: gas chromatograph; the chromatographic column is DB-WAX (30m×0.53mm×1.0μm) capillary column; using FID detector, the initial temperature of the chromatographic column is 35-45°C, the holding time is 8-12min, and then the temperature is raised to 80°C at a rate of 8-12°C/min, and then the final temperature of the column is raised to 250°C at a rate of 35-45°C/min. The time is 2-5min; the carrier gas is nitrogen, the carrier gas flow rate is 2.5-3.5ml/min, the split ratio is 20:1; the inlet temperature is 190-210°C, the detector temperature is 240-260°C; the sampling method is headspace injection, the equilibrium temperature is 90°C, the loop temperature is 100°C, the transfer line temperature is 110°C, and the equilibrium time is 30min; the injection volume is 1.0mL.

2)配制溶液,配制下列溶液:2) Prepare the solution and prepare the following solutions:

a.空白溶液(稀释剂):二甲基亚砜;a. blank solution (diluent): dimethyl sulfoxide;

b.对照品溶液:称取丙酮0.5g、二氯甲烷0.06g、四氢呋喃0.072g、乙酸乙酯0.5g、甲苯0.089g、乙醚0.5g、乙腈0.041g、二氟溴乙酸乙酯0.1g,置50ml量瓶中,用稀释剂稀释至刻度,摇匀,作为储备液;移取储备液2.0ml,置100ml量瓶中,用稀释剂稀释至刻度,摇匀,再精密量取5.0ml置20ml顶空瓶中,加盖密封。C.供试品溶液:取α-核糖甲磺酸酯0.2g,置20ml顶空瓶中,加5.0ml稀释剂溶解,加盖密封,摇匀,即得,平行配2份。b. Reference substance solution: Weigh 0.5g of acetone, 0.06g of dichloromethane, 0.072g of tetrahydrofuran, 0.5g of ethyl acetate, 0.089g of toluene, 0.5g of diethyl ether, 0.041g of acetonitrile, and 0.1g of ethyl difluorobromoacetate, put them in a 50ml measuring bottle, dilute to the mark with a diluent, shake well, and use it as a stock solution; pipette 2.0ml of the stock solution and put it in a 100ml measuring bottle , dilute to the mark with a diluent, shake well, then accurately measure 5.0ml, place it in a 20ml headspace bottle, and seal it with a cap. C. The test solution: take 0.2g of α-ribose mesylate, put it in a 20ml headspace bottle, add 5.0ml of diluent to dissolve, seal it with a cap, shake well, and prepare 2 parts in parallel.

按下述序列表进样:Inject samples according to the following sequence table:

名称name 进样针数Number of needles 空白溶液blank solution ≥1针≥1 needle 对照品溶液Reference solution 6针6 pins 供试品溶液Test solution 各进1针1 stitch each

α-核糖甲磺酸酯供试品溶液中各个溶剂按加外标法以峰面积计算。Each solvent in the α-ribose mesylate solution of the test product is calculated by the peak area by adding an external standard method.

优选地,本发明所述气相色谱分析选定的色谱条件如下:Preferably, the selected chromatographic conditions for gas chromatography analysis of the present invention are as follows:

采用FID检测器;Using FID detector;

色谱柱:DB-WAX(30m×0.53mm×1.0μm)毛细管色谱柱;Chromatographic column: DB-WAX (30m×0.53mm×1.0μm) capillary column;

程序升温:起始温度为40℃,维持10分钟,以每分钟10℃升温至80℃,再以每分钟40℃升温至250℃维持3分钟。Programmed temperature rise: the initial temperature is 40°C, maintained for 10 minutes, raised to 80°C at a rate of 10°C per minute, and then raised to 250°C at a rate of 40°C per minute and maintained for 3 minutes.

载气:氮气,流速为3.0mL/min,分流比:20:1;Carrier gas: nitrogen, flow rate 3.0mL/min, split ratio: 20:1;

进样口温度:200℃;Injection port temperature: 200°C;

检测器(FID)温度:250℃;Detector (FID) temperature: 250°C;

进样方式:顶空进样,平衡温度90℃,定量环温度100℃,传输线温度110℃,平衡时间30min;Sampling method: headspace sampling, equilibration temperature 90°C, quantitative loop temperature 100°C, transfer line temperature 110°C, equilibration time 30min;

进样体积:1.0ml。Injection volume: 1.0ml.

本发明的有益效果如下:The beneficial effects of the present invention are as follows:

本发明能有效可以有效分离α-核糖甲磺酸酯中残留溶剂并能定量检测其含量,残留溶剂为乙醚、丙酮、四氢呋喃、乙酸乙酯、二氯甲烷、乙腈、甲苯、二氟溴乙酸乙酯中的一种或二种以上,该方法操作简便,专属性强,灵敏度、准确度高,从而确保α-核糖甲磺酸酯质量可控,目前对于α-核糖甲磺酸酯中多种残留溶剂的检测方法还没有报道,本发明可为α-核糖甲磺酸酯中残留溶剂检测提供一种可靠的检测方法,适于全面推广和应用。The present invention can effectively separate the residual solvent in α-ribose mesylate and quantitatively detect its content. The residual solvent is ether, acetone, tetrahydrofuran, ethyl acetate, dichloromethane, acetonitrile, toluene, and ethyl difluorobromoacetate. The detection of residual solvents in ribose mesylate provides a reliable detection method, which is suitable for general promotion and application.

附图说明Description of drawings

图1为空白溶液色谱图;Fig. 1 is blank solution chromatogram;

图2为对照品溶液色谱图;Fig. 2 is reference substance solution chromatogram;

图3为供试品溶液色谱图;Fig. 3 is need testing solution chromatogram;

图4为各溶剂线性测试结果图;Fig. 4 is each solvent linearity test result figure;

图5为准确度溶液色谱图。Fig. 5 is the accuracy solution chromatogram.

具体实施方式Detailed ways

本发明将结合实施例(附图)对上述内容作进一步补充说明,但不应该理解为本发明范围仅限于以下实例。The present invention will further supplement the above content with reference to the embodiments (accompanying drawings), but it should not be understood that the scope of the present invention is limited to the following examples.

以下实施例中采用的仪器和色谱条件如下:The instrument and chromatographic conditions adopted in the following examples are as follows:

气相色谱仪为Agilent7890A,采用FID检测器,柱初始温度为35-45℃,保持时间为8-12min,然后以8-12℃/min的升温速率升至80℃,再以35-45℃/min的升温速率升至柱最终温度为250℃,柱最终温度保持时间为2-5min;载气为氮气,优选的,所述载气流速为2.5-3.5ml/min,分流比为20:1;进样口温度为190-210℃,检测器温度为240-260℃;进样方式为顶空进样,平衡温度90℃,定量环温度100℃,传输线温度110℃,平衡时间30min;进样体积为1.0mL。The gas chromatograph is Agilent7890A, using FID detector, the initial temperature of the column is 35-45°C, the holding time is 8-12min, then it is raised to 80°C at a heating rate of 8-12°C/min, and then the final temperature of the column is raised to 250°C at a heating rate of 35-45°C/min, and the holding time of the final temperature of the column is 2-5min; the carrier gas is nitrogen. The flow ratio is 20:1; the inlet temperature is 190-210°C, the detector temperature is 240-260°C; the injection method is headspace injection, the equilibrium temperature is 90°C, the quantitative loop temperature is 100°C, the transfer line temperature is 110°C, and the equilibration time is 30 minutes; the injection volume is 1.0mL.

实施例1Example 1

专属性考察,如图1~图2,图5所示:Specificity investigation, as shown in Figure 1-2 and Figure 5:

精密量取空白溶液,对照品溶液、各杂质定位溶液各1.0mL,注入气色谱仪,记录色谱图。各杂质定位及分离度实验结果显示,空白无干扰,其他溶剂对样品测定无干扰,其相邻溶剂之间最小分离度为2.60,本分析条件专属性良好,测试结果如下:Precisely measure 1.0 mL of the blank solution, the reference solution, and each impurity positioning solution, inject them into the gas chromatograph, and record the chromatograms. The results of the impurity location and resolution experiments show that the blank has no interference, and other solvents have no interference to the sample determination, and the minimum resolution between adjacent solvents is 2.60. The specificity of the analysis conditions is good, and the test results are as follows:

实施例2Example 2

灵敏度试验考察结果:Sensitivity test investigation results:

定量限(LOQ)结果如下:The limit of quantitation (LOQ) results are as follows:

检测限(LOD)结果如下:The limit of detection (LOD) results are as follows:

各溶剂的定量限、检测限测定结果显示:各个溶剂检测灵敏度高(远高于限度标准值),方法灵敏度符合要求。The determination results of quantification limit and detection limit of each solvent show that each solvent has high detection sensitivity (far higher than the limit standard value), and the sensitivity of the method meets the requirements.

实施例3Example 3

线性考察,如图4所示:Linear investigation, as shown in Figure 4:

以峰面积对浓度作图,乙醚在浓度40.664μg/mL-304.980μg/mL范围内,丙酮在浓度40.120μg/mL-300.900μg/mL范围内,四氢呋喃在浓度5.928μg/mL-44.460μg/mL范围内,乙酸乙酯在浓度40.160μg/mL-301.200μg/mL范围内,二氯甲烷在浓度5.128μg/mL-38.460μg/mL范围内,乙腈在浓度3.232μg/mL-24.240μg/mL范围内,甲苯在浓度7.016μg/mL-52.620μg/mL范围内,二氟溴乙酸乙酯在浓度8.792μg/mL-65.940μg/mL范围内,样品浓度与峰面积成线性关系,线性良好,具体结果如下:The peak area is plotted against the concentration, the concentration of ether is in the range of 40.664μg/mL-304.980μg/mL, the concentration of acetone is in the range of 40.120μg/mL-300.900μg/mL, the concentration of tetrahydrofuran is in the range of 5.928μg/mL-44.460μg/mL, and the concentration of ethyl acetate is in the range of 40.160μg/mL-301.200μg In the range of 5.128μg/mL-38.460μg/mL for dichloromethane, in the range of 3.232μg/mL-24.240μg/mL for acetonitrile, in the range of 7.016μg/mL-52.620μg/mL for toluene, in the range of 8.792μg/mL-65.940μg/mL for ethyl difluorobromoacetate, the sample concentration and The peak area has a linear relationship, and the linearity is good. The specific results are as follows:

名称name 线性方程linear equation R2 R 2 乙醚Ether y=0.2849x-1.0310y=0.2849x-1.0310 0.99930.9993 丙酮acetone y=0.0526x-0.2046y=0.0526x-0.2046 0.99960.9996 四氢呋喃Tetrahydrofuran y=0.0698x-0.0407y=0.0698x-0.0407 0.99960.9996 乙酸乙酯ethyl acetate y=0.0393x-0.1650y=0.0393x-0.1650 0.99960.9996 二氯甲烷Dichloromethane y=0.0116x-0.0067y=0.0116x-0.0067 0.99950.9995 乙腈Acetonitrile y=0.0154x-0.0052y=0.0154x-0.0052 0.99870.9987 甲苯toluene y=0.0532x-0.0527y=0.0532x-0.0527 0.99940.9994 二氟溴乙酸乙酯Ethyl difluorobromoacetate y=0.0046x-0.0058y=0.0046x-0.0058 0.99930.9993

实施例4Example 4

准确度考察,色谱图如图5所示:Accuracy inspection, the chromatogram is shown in Figure 5:

分别按乙醚、丙酮、四氢呋喃、乙酸乙酯、二氯甲烷、乙腈、甲苯、二氟溴乙酸乙酯的限度浓度50%、100%、150%加样配制回收率溶液,每组浓度平行配制3份,同时配制一份供试品溶液和一份对照品溶液,按照上述色谱条件测定,计算回收率。各溶剂回收率均在90%-110%范围内,结果见下表:Respectively add samples to prepare recovery rate solutions according to the limit concentrations of ether, acetone, tetrahydrofuran, ethyl acetate, dichloromethane, acetonitrile, toluene, and ethyl difluorobromoacetate at 50%, 100%, and 150%. Prepare 3 parts in parallel for each group of concentrations, prepare a part of the test solution and a part of the reference solution at the same time, measure according to the above-mentioned chromatographic conditions, and calculate the recovery rate. Each solvent recovery rate is in the range of 90%-110%, the results are shown in the following table:

实施例5Example 5

耐用性考察,分别更换色谱柱、改变初始柱温(40±1℃)、载气流速(3.0±0.1ml/min)、进样口温度(200±2℃)、升温速率(±1℃/min),对对照品溶液中各溶剂峰面积的RSD及各溶剂出峰的最小分离度结果进行比较,考察其耐用性。改变色谱条件参数,对照品溶液中各溶剂6针峰面积最大RSD为6.7%,小于10%;系统适用性溶液的分离度均大于1.5,说明该方法耐用性良好。结果见下表:To inspect the durability, replace the chromatographic column, change the initial column temperature (40±1°C), carrier gas flow rate (3.0±0.1ml/min), injection port temperature (200±2°C), and heating rate (±1°C/min), compare the RSD of the peak area of each solvent in the reference solution and the minimum resolution of each solvent’s peak separation, and investigate its durability. Changing the parameters of the chromatographic conditions, the maximum RSD of the 6-pin peak area of each solvent in the reference solution was 6.7%, which was less than 10%. The results are shown in the table below:

以上所述仅是本发明的优选实施方式,应当指出,本技术领域人员应当明了,在不脱离本发明原理的前提下,还可以作出若干改进,这些改进也应视为本发明的保护范围,不应视为对本发明的具体限制。The above is only a preferred embodiment of the present invention. It should be pointed out that those skilled in the art should understand that some improvements can be made without departing from the principles of the present invention.

Claims (5)

1. A method for detecting residual solvent in alpha-ribose mesylate by gas chromatography, comprising the steps of:
1) Selection of instrument and chromatographic conditions: a gas chromatograph; the chromatographic column is DB-WAX (30 m×0.53mm×1.0 μm) capillary chromatographic column; using a FID detector;
1) Preparation of a control solution: weighing 0.5g of acetone, 0.06g of dichloromethane, 0.072g of tetrahydrofuran, 0.5g of ethyl acetate, 0.089g of toluene, 0.5g of diethyl ether, 0.041g of acetonitrile and 0.1g of difluorobromoacetic acid ethyl ester, placing into a 50ml measuring flask, diluting to a scale with a diluent, shaking uniformly to serve as a stock solution, transferring 2.0ml of the stock solution, placing into a 100ml measuring flask, diluting to the scale with the diluent, shaking uniformly, precisely weighing 5.0ml of the stock solution, placing into a 20ml overhead flask, and sealing by capping;
2) Preparation of test solution: taking 0.2g of alpha-ribose mesylate, placing the alpha-ribose mesylate into a 20ml headspace bottle, adding 5.0ml of diluent for dissolution, capping, sealing and shaking uniformly to obtain the finished product;
3) Determination of residual solvent: taking a reference substance solution and a sample solution, carrying out headspace sampling, carrying out gas chromatography analysis to obtain peak areas of all solvents, and calculating according to an external standard method by the peak areas to obtain the chromatographic column temperature change flow in gas phase detection, wherein the chromatographic column temperature change flow is as follows: the initial temperature of the chromatographic column is 35-45 ℃, the retention time is 8-12min, then the temperature is increased to 80 ℃ at the heating rate of 8-12 ℃/min, and the final temperature of the chromatographic column is 250 ℃ at the heating rate of 35-45 ℃/min, and the retention time of the final temperature of the chromatographic column is 2-5min.
2. The method for detecting residual solvent in α -ribose mesylate by gas chromatography according to claim 1, wherein the diluent is dimethyl sulfoxide solution.
3. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the carrier gas in the gas chromatography detection is nitrogen, the flow rate of the carrier gas is 2.5-3.5ml/min, and the split ratio is 20:1.
4. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the temperature of the sample inlet in the gas chromatography detection is 190-210 ℃, and the temperature of the detector is 240-260 ℃.
5. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the sample injection mode in the gas chromatography detection is headspace sample injection, the equilibrium temperature is 90 ℃, the quantitative loop temperature is 100 ℃, the transmission line temperature is 110 ℃, the equilibrium time is 30min, and the sample injection volume is 1.0mL.
CN202310195703.3A 2023-03-03 2023-03-03 A method for detecting residual solvent in alpha-ribose methanesulfonate by gas chromatography Active CN116465985B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310195703.3A CN116465985B (en) 2023-03-03 2023-03-03 A method for detecting residual solvent in alpha-ribose methanesulfonate by gas chromatography

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310195703.3A CN116465985B (en) 2023-03-03 2023-03-03 A method for detecting residual solvent in alpha-ribose methanesulfonate by gas chromatography

Publications (2)

Publication Number Publication Date
CN116465985A true CN116465985A (en) 2023-07-21
CN116465985B CN116465985B (en) 2024-12-10

Family

ID=87181347

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310195703.3A Active CN116465985B (en) 2023-03-03 2023-03-03 A method for detecting residual solvent in alpha-ribose methanesulfonate by gas chromatography

Country Status (1)

Country Link
CN (1) CN116465985B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106008340A (en) * 2015-03-24 2016-10-12 上海璎黎药业有限公司 Condensed ring derivative, preparation method, intermediate, pharmaceutical composition and application thereof
CN108318615A (en) * 2018-03-16 2018-07-24 湖北亿诺瑞生物制药有限公司 The method that headspace gas chromatography detects residual solvent in heparin sodium
CN108614058A (en) * 2018-06-19 2018-10-02 广西壮族自治区食品药品检验所 Measure the headspace gas chromatography of glycine organic solvent residual in raw medicine amount

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106008340A (en) * 2015-03-24 2016-10-12 上海璎黎药业有限公司 Condensed ring derivative, preparation method, intermediate, pharmaceutical composition and application thereof
CN108318615A (en) * 2018-03-16 2018-07-24 湖北亿诺瑞生物制药有限公司 The method that headspace gas chromatography detects residual solvent in heparin sodium
CN108614058A (en) * 2018-06-19 2018-10-02 广西壮族自治区食品药品检验所 Measure the headspace gas chromatography of glycine organic solvent residual in raw medicine amount

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
CHANDRAKANT SOJITRA 等: "Development and validation of residual solvent determination by headspace gas chromatography in Imatinib Mesylate API", SN APPLIED SCIENCES, vol. 01, no. 03, 14 February 2019 (2019-02-14), pages 1 - 9 *
彭洁 等: "顶空气相色谱法测定卡维地洛中有机溶剂残留", 广东药学院学报, vol. 23, no. 05, 31 October 2007 (2007-10-31), pages 536 - 538 *
杜薇 等: "静态顶空气相色谱法测定盐酸西那卡塞中的残留溶剂", 华西药学杂志, vol. 28, no. 03, 30 June 2013 (2013-06-30), pages 290 - 292 *
杨建云 等: "毛细管气相色谱法测定异黄酮衍生物2702中有机溶剂残留量", 科学技术与工程, vol. 08, no. 23, 1 December 2008 (2008-12-01), pages 6328 - 6330 *
由亚宁 等: "顶空气相色谱法测定丹参素冰片酯脂肪乳中溶剂残留量", 西北药学杂志, vol. 28, no. 04, 31 July 2013 (2013-07-31), pages 357 - 359 *
范志先 等: "27种有机溶剂的气相色谱同时分析", 青岛科技大学学报(自然科学版), vol. 29, no. 06, 15 December 2008 (2008-12-15), pages 497 - 499 *

Also Published As

Publication number Publication date
CN116465985B (en) 2024-12-10

Similar Documents

Publication Publication Date Title
CN104655751B (en) A kind of detect the method for organic solvent residual in dapoxetine
CN106153749A (en) The method of residual solvent in inspection chlophedianol hydrochloride Starting material medicine
WO2021022876A1 (en) Method for determining halogenated acid content in chloral hydrate or preparation thereof
WO2023065521A1 (en) Gas chromatography-mass spectrometry combined method for determining genotoxic impurity 1,3-dichloro-2-propanol
CN112710758A (en) Method for detecting residual solvent in tapentadol hydrochloride raw material medicine
CN116465985A (en) Method for detecting residual solvent in alpha-ribose mesylate by gas chromatography
CN108982706B (en) Method for detecting impurity cis-perhydroisoindole in mitiglinide calcium
CN103424497B (en) Detection method of isobutyl chloroformate
CN114518413B (en) A method for determining the content of proline in captopril bulk drug
CN109507350A (en) A kind of 2- cyano -4 '-bromomethylbiphenyl content method in measurement ethyl ester of candesartan
CN114965749A (en) Detection method of related substances in sulpiride bulk drug
CN112697934A (en) Method for detecting content of pyroglutamic acid in compound amino acid injection
CN110187023A (en) A kind of method of inspection of the razaxaban in relation to substance
CN116338051A (en) Analysis method for content of chloroethane in isosorbide mononitrate
CN112305100B (en) Method for detecting content of genotoxic impurity benzyl bromide in medicine
CN113777204B (en) Detection method of p-hydroxyacetophenone related substances
CN110824038A (en) Liquid chromatography analysis method of 2,3,4, 6-tetra-O-trimethylsilyl-D-gluconolactone
CN119000964B (en) A gas phase analysis method for N-(3-cyclohexene-1-ylmethyl)-4-aminopiperidine residue
CN118961964A (en) A method for determining the residual amount of organic solvent in siponimod by headspace capillary gas chromatography
CN115980201A (en) A method for measuring residual piperidine
CN112684045A (en) Method for determining and analyzing content of main drug in ubenimex solid preparation
CN119959391A (en) A method for detecting sulfonate impurities in drugs and its application
CN119595815A (en) Method for detecting L-pyroglutamic acid and methionine sulfoxide in compound amino acid injection
CN119757614A (en) A gas phase analysis method for detecting side chain residues in pivmecillin hydrochloride
CN115980226A (en) A kind of assay method of trichloromethane residue in nifedione

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant