Yadav Anant D, Alaspure Ashish C, Bhavsar Pinal S, Lodha Sandesh R, Gore Anil H
Tarsadia Institute of Chemical Science, Uka Tarsadia University, Bardoli, Gujarat, India.
Analytical Research and Development, Alkem Laboratories Ltd., Bharuch, Gujarat, India.
Rapid Commun Mass Spectrom. 2025 Dec 15;39(23):e10126. doi: 10.1002/rcm.10126.
Nitrosamine impurities, such as N-nitroso diethylamine (NDEA), N-nitroso dimethylamine (NDMA), and 1-nitroso piperazine (1-NP), have raised serious health concerns due to their carcinogenic and mutagenic properties. The pharmaceutical industry faces increasing regulatory pressure to monitor these compounds at trace levels. This study addresses the need for a robust analytical method to ensure the safety of lurasidone hydrochloride (LUR), an antipsychotic drug.
A sensitive and specific LC-MS/MS method was developed using atmospheric pressure chemical ionization (APCI) in positive mode and operated in multiple reaction monitoring (MRM). Chromatographic separation was performed on a Sapphirus C18 HP-classic column under gradient elution, with 0.1% formic acid in water and methanol as the mobile phase. Detection was carried out using an Agilent 6470B triple-quadrupole mass spectrometer.
The method demonstrated excellent linearity (regression coefficient > 0.999) across a range extending to 200% of the specified limit. Limits of detection and quantitation were suitable for trace-level analysis. Accuracy was confirmed through recovery studies, with results ranging between 80 and 120%. The method met ICH Q2 (R2) validation criteria, ensuring reliability for regulatory use.
The developed APCI-LC-MS/MS method provides accurate and reproducible quantification of NDEA, NDMA, and 1-NP in lurasidone hydrochloride. Its sensitivity and compliance with regulatory standards make it suitable for routine quality control and stability testing of nitrosamine impurities in lurasidone hydrochloride drug substance.
亚硝胺杂质，如N-亚硝基二乙胺（NDEA）、N-亚硝基二甲胺（NDMA）和1-亚硝基哌嗪（1-NP），因其致癌和致突变特性引发了严重的健康问题。制药行业面临着越来越大的监管压力，需要对这些痕量水平的化合物进行监测。本研究满足了对一种可靠分析方法的需求，以确保抗精神病药物盐酸鲁拉西酮（LUR）的安全性。
开发了一种灵敏且特异的液相色谱-串联质谱（LC-MS/MS）方法，采用大气压化学电离（APCI）正模式并在多反应监测（MRM）模式下运行。在Sapphirus C18 HP-classic柱上进行梯度洗脱色谱分离，以含0.1%甲酸的水和甲醇作为流动相。使用安捷伦6470B三重四极杆质谱仪进行检测。
该方法在高达规定限度200%的范围内显示出优异的线性（回归系数>0.999）。检测限和定量限适用于痕量水平分析。通过回收率研究确认了准确性，结果在80%至120%之间。该方法符合国际人用药品注册技术协调会（ICH）Q2（R2）验证标准，确保了监管用途的可靠性。
所开发的APCI-LC-MS/MS方法能够准确、可重复地定量盐酸鲁拉西酮中的NDEA、NDMA和1-NP。其灵敏度和符合监管标准使其适用于盐酸鲁拉西酮原料药中亚硝胺杂质的常规质量控制和稳定性测试。
