Department of Chemistry, Koneru Lakshmaiah Education Foundation, Aziznagar, Hyderabad, Telangana 500075, India.
Shenzhen DEC Pharmaceutical Co., Ltd, Analytical Development Department, Shenzhen 518000, China.
J AOAC Int. 2024 Nov 1;107(6):921-933. doi: 10.1093/jaoacint/qsae061.
Class-I residual solvents such as 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, 1,2-dichloroethane are toxic, environmental hazards, and carcinogenic to humans. A headspace-gas chromatography-mass spectrometer is a sophisticated instrument for the quantification of residual solvents at lower limits.
An exact, sensitive, reliable, and fast method was developed to determine 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, and 1,2-dichloroethane present in different drug substances using a headspace-gas chromatography-mass spectrometer.
Helium is used as a carrier gas. N-methyl-2-pyrrolidone is used as a diluent, and the stationary phase is a DB-624 (60 m × 0.25 mm × 1.4 μm film thickness) column with a flow rate of 1.5 mL/min.
The concentration LODs for 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, and 1,2-dichloroethane were 0.24, 5, 0.12, 0.06, and 0.15 ppm. The concentrations LOQs for the aforementioned impurities were 0.8, 15, 0.4, 0.2, and 0.5 ppm. The linearity was assessed over the range from LOQ to 120% of the specification level.
The current method's system suitability, precision, linearity, and accuracy parameters were assessed in accordance with the United states pharmacopeia (USP) < 1225> and International Conference on Harmonization of technical standards for the registration of medicines for human use (ICH) Q2(R2), and the results were within the acceptance criteria.
No research studies have been reported on determining class-I residual solvents in lincomycin hydrochloride, dapagliflozin, vonoprazan fumarate, and telmisartan drug substances. The proposed research aims to develop a common method for the quantification of class-I residual solvents for drug substances. The quality by design (QbD) concept is utilized in performance verification.
1,1-二氯乙烯、1,1,1-三氯乙烷、四氯化碳、苯、1,2-二氯乙烷等 I 类残留溶剂对人体具有毒性、环境危害性和致癌性。顶空-气相色谱-质谱联用仪是一种用于定量检测低浓度残留溶剂的精密仪器。
开发一种准确、灵敏、可靠和快速的方法，用于使用顶空-气相色谱-质谱联用仪测定不同药物中的 1,1-二氯乙烯、1,1,1-三氯乙烷、四氯化碳、苯和 1,2-二氯乙烷。
使用氦气作为载气，N-甲基-2-吡咯烷酮作为稀释剂，固定相为 DB-624（60m×0.25mm×1.4μm 膜厚）柱，流速为 1.5mL/min。
1,1-二氯乙烯、1,1,1-三氯乙烷、四氯化碳、苯和 1,2-二氯乙烷的浓度检测限分别为 0.24、5、0.12、0.06 和 0.15ppm。上述杂质的浓度定量限分别为 0.8、15、0.4、0.2 和 0.5ppm。线性度在从 LOQ 到规格水平 120%的范围内进行评估。
根据美国药典（USP）<1225>和人用药品注册技术要求国际协调会议（ICH）Q2（R2），对当前方法的系统适用性、精密度、线性度和准确度参数进行了评估，结果均在可接受标准范围内。
目前尚未有研究报道测定盐酸林可霉素、达格列净、伏诺拉生富马酸盐和替米沙坦药物中 I 类残留溶剂。本研究旨在开发一种用于测定药物中 I 类残留溶剂的通用方法。质量源于设计（QbD）概念用于性能验证。
