[1]杨镇伟,林琪,吴振,等.米诺膦酸原料药中4种有机残留溶剂的毛细管气相色谱法测定[J].华侨大学学报(自然科学版),2022,43(1):96-101.[doi:10.11830/ISSN.1000-5013.202102004]
　YANG Zhenwei,LIN Qi,WU Zhen,et al.Capillary Gas Chromatography Determination of Four Organic Residual Solvents in Minodronic Acid Bulk Drugs[J].Journal of Huaqiao University(Natural Science),2022,43(1):96-101.[doi:10.11830/ISSN.1000-5013.202102004]
点击复制

米诺膦酸原料药中4种有机残留溶剂的毛细管气相色谱法测定()
分享到：

《华侨大学学报（自然科学版）》[ISSN:1000-5013/CN:35-1079/N]

卷:
第43卷
期数:
2022年第1期
页码:
96-101
栏目:
出版日期:
2022-01-09

文章信息/Info

Title:
Capillary Gas Chromatography Determination of Four Organic Residual Solvents in Minodronic Acid Bulk Drugs
文章编号:
1000-5013(2022)01-0096-06
作者:
杨镇伟1;  林琪1;  吴振2;  刘智阳3;  王立强1
1. 华侨大学 生物医学学院, 福建 泉州 362021;2. 厦门大学 药学院, 福建 厦门 361102;3. 中铭生物(深圳)集团有限公司, 广东 深圳 518101
Author(s):
YANG Zhenwei1;  LIN Qi1;  WU Zhen2;  LIU Zhiyang3;  WANG Liqiang1
1. School of Medicine, Huaqiao University, Quanzhou 362021, China; 2. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; 3. Zhongming Biology(Shenzhen)Group Company Limited, Shenzhen 518101, China
关键词:
米诺膦酸;  残留溶剂;  毛细管气相色谱法;  N; N-二甲基甲酰胺
Keywords:
minodronic acid;  residual organic solvent;  capillary gas chromatography method;  N; N-dimethylformamide
分类号:
R917
DOI:
10.11830/ISSN.1000-5013.202102004
文献标志码:
A
摘要:
建立对米诺膦酸原料药中的乙醇、甲醇、二氯甲烷、甲苯等4种残留溶剂含量的毛细管气相色谱测定方法.采用安捷伦DB-624(0.32 mm×30 m, 3 μm)色谱柱,固定液为6%氰丙基苯基+94%二甲基聚硅氧烷,载气为N2,检测器为火焰离子化检测仪(FID),进样口温度为250 ℃,检测器温度为200 ℃,柱温为程序升温,初始温度40 ℃,保持3 min,以每分钟15 ℃升温至200 ℃,并保持10 min;以N,N-二甲基甲酰胺作为主要溶剂,采用直接进样法测定4种溶剂的残留量.结果表明:4种残留溶剂的色谱峰分离度良好,在一定范围内呈良好线性关系(R2>0.998),乙醇、甲醇、二氯甲烷和甲苯的检测限分别为0.029,0.052,0.051,0.051 ng,平均回收率均在96.71%~112.37%的范围内,相对标准偏差(RSD)均小于5%;米诺膦酸3批小试样品中均未检出乙醇、甲醇、二氯甲烷和甲苯等4种残留溶剂.本检测方法灵敏度高、准确度良好,可作为米诺膦酸原料药中有机溶剂残留量的检测方法.
Abstract:
A capillary gas chromatography method was established for the determination of 4 organic residual solvents( ethanol, methanol,dichloromethane,and toluene )in minodronic acid bulk drugs. The Agilent DB624(0.32 mm×30 m, 3 μm)chromatographic column was used and the parameters were set as: the stationary liquid was 6% cyanopropylphenyl-94% dimethylpolysiloxane, the carrier gas was N2, the detector was flame ionization detector(FID), the injection port temperature was 250 ℃, the detector temperature was 200 ℃, the column temperature was programmed with the initial temperature 40 ℃(maintained for 3 min), and the temperature was increased to 200 ℃ at 15 ℃ per minute and maintained for 10 min. Using N,N-dimethylformamide as the main solvent, the residual of 4 organic solvents was determined by direct injection method. The results show that the chromatographic peaks of the four organic solvents were well separated. It has a good linear relationship in a certain range(R2>0.998),and the detection limits of ethanol, methanol, dichloromethane and toluene were 0.029,0.052, 0.051, 0.051 ng, respectively. The average recoveries were in the range of 96.71%-112.37% with relative standard deviation(RSD)less than 5%. Four residual solvents, including ethanol, methanol, dichloromethane and toluene were not detected in 3 batches of minodronic acid samples. This detection method has high sensitivity and accuracy, and can be used as a detection method for residual organic solvents in minodronic acid bulk drugs.

参考文献/References:

[1] KITAMURA N,SHIRAIWA H,INOMATA H,et al.Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis[J].Int J Rheum Dis,2018,21(4):813-820.DOI:10.1111/1756-185X.12844.
[2] 宋伟杰,曾皓月,龙莎,等.采用原研制剂制备米诺膦酸片及体外溶出度的一致性考察[J].华侨大学学报(自然科学版),2018,39(1):70-74.DOI:10.11830/ISSN.1000-5013.201706032.
[3] TANAKA M,HOSOYA A,MORI H,et al.Minodronic acid induces morphological changes in osteoclasts at bone resorption sites and reaches a level required for antagonism of purinergic P2X2/3 receptors[J].J Bone Miner Metab,2018,36(1):54-63.DOI:10.1007/s00774-017-0814-y.
[4] TAGUCHI A,UEMURA Y,IMAI T,et al.Incidence of osteonecrosis of the jaw in Japanese osteoporosis patients taking minodronic acid[J].J Bone Miner Metab,2019,37(5):886-892.DOI:10.1007/s00774-019-00990-5.
[5] DUNFORD J E,THOMPSON K,COXON F P,et al.Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates[J].J Pharmacol Exp Ther,2001,296(2):235-242.
[6] 华小懿,沈于兰,杨敏智.离子色谱法测定米诺膦酸及其片剂的含量[J].中国药品标准,2019,20(2):138-142.DOI:10.19778/j.chp.2019.02.008.
[7] 宋伟杰,周玥莹,王立强,等.高效液相色谱法测定米诺膦酸的含量及有关物质[J].中国新药杂志,2018,27(16):1932-1938.
[8] 邬方宁.高效液相色谱法测定米诺膦酸片中米诺膦酸[J].现代药物与临床,2011,26(1):66-67.
[9] 邵宪伟.米诺膦酸的合成工艺研究[D].北京:北京化工大学,2017.
[10] 赵世明,李玲,韩世磊,等.米诺膦酸的合成[J].中国新药杂志,2014,23(11):1307-1310.
[11] 吴素平,蔡玲,金坚,等.顶空气相色谱法检测米诺膦酸中残留溶剂[J].中国新药杂志,2016,25(24):2839-2842.
[12] 张巍,蔡犇,李范珠.顶空气相色谱法测定依帕司他有机溶剂残留量[J].中国现代应用药学.2017,34(9):1286-1288.DOI:10.13748/j.cnki.issn1007-7693.2017.09.015.
[13] 裴丽娟,田晨,齐然然,等.顶空气相色谱法同时测定布南色林原料药中9种有机溶剂的残留量[J].中国药房,2017,28(12):1699-1702.DOI:10.6039/j.issn.1001-0408.2017.12.32.
[14] 袁淑杰.新型杂环双膦酸类化合物米诺膦酸的合成新工艺研究[J].中国医药指南,2015,13(5):291-292.DOI:10.15912/j.cnki.gocm.2015.05.220.
[15] RYAN A E.Protecting the rights of pediatric research subjects in the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use[J].Fordham International Law Journal.2000,23(3):848-934.DOI:10.1007/s11270-010-0628-1.
[16] 国家药典委员会.中华人民共和国药典: 四部(2020年版)[M].北京:中国医药科技出版社,2020.

备注/Memo

备注/Memo:
收稿日期: 2021-02-02
通信作者: 王立强(1970-),男,教授,博士,主要从事药剂学和创新药物的研究.E-mail:wlq1599@163.com.
基金项目: 国家重点研发计划项目(2016YFE0101700); 福建省高校产学合作项目(2019Y4007); 福建省泉州市科技计划项目(2020SY001); 华侨大学研究生科研创新能力培育计划项目(18013071019)http://www.hdxb.hqu.edu.cn
更新日期/Last Update: 2022-01-20