Department of Chemistry, Mithibai College Of Arts, Chauhan Institute of Science & Amrutben Jivanlal College Of Commerce And Economics, Vile Parle West, Mumbai 400056, India.
Department of Chemistry, Mithibai College Of Arts, Chauhan Institute of Science & Amrutben Jivanlal College Of Commerce And Economics, Vile Parle West, Mumbai 400056, India.
J Chromatogr A. 2024 Sep 13;1732:465176. doi: 10.1016/j.chroma.2024.465176. Epub 2024 Jul 18.
This research summaries the development, optimization and validation of liquid chromatography tandem mass spectrometric (LC-MS/MS) method for concurrent measurement of seven nitrosamines viz; NDMA, NDEA, NDIPA, NDPA, NEIPA, NMPA & NMBA in Olmesartan tablet. Controlling these nitrosamines at trace levels is imperative for ensuring the safety of drug substances and products for consumption. Various regulatory authorities stress the significance of utilizing highly sensitive analytical methods to precisely measure nitrosamines at trace levels. The method applied effective chromatographic separation and optimized parameters for mass spectrometric detection. Detection was carried out using APCI positive ion mode. Chromatographic separation was achieved using a Thermo Accucore PFP column (150 mm x 4.6 mm, 2.6 µ), with a simple gradient elution of mobile phase consisting of 0.1 % formic acid in water (mobile phase A) and methanol (mobile phase B). The total run time was 20 min, with a flow rate of 0.800 mL/min. The method was validated according to the International Council on Harmonisation (ICH Q2 (R2)) guidelines. The established method demonstrated excellent linearity (R> 0.99) and sensitivity for all the nitrosamines. Detection and quantification limits were sufficiently low for trace nitrosamine levels having good S/N ratio. The method showed good accuracy in Olmesartan tablet samples, with recoveries ranges between 80 % to 120 %. The new analytical approach has exceptional repeatability and reliability, making it possible to precisely quantify the levels of seven nitrosamines in Olmesartan medoxomil tablets in a single analytical run.
本研究总结了液相色谱-串联质谱（LC-MS/MS）法同时测定奥美沙坦片中 7 种亚硝胺（NDMA、NDEA、NDIPA、NDPA、NEIPA、NMPA 和 NMBA）的开发、优化和验证。控制这些痕量亚硝胺对于确保药物物质和产品的消费安全至关重要。各监管机构强调必须利用高灵敏度的分析方法，精确测量痕量亚硝胺。该方法应用了有效的色谱分离和优化的质谱检测参数。检测采用 APCI 正离子模式。色谱分离采用 Thermo Accucore PFP 柱（150mm×4.6mm，2.6μm），以水（流动相 A）中的 0.1%甲酸和甲醇（流动相 B）的简单梯度洗脱进行。总运行时间为 20min，流速为 0.800mL/min。该方法按照国际协调会议（ICH Q2（R2））指南进行了验证。所建立的方法对所有亚硝胺均表现出优异的线性（R＞0.99）和灵敏度。检测限和定量限足够低，具有良好的 S/N 比，可用于痕量亚硝胺水平。该方法在奥美沙坦片中表现出良好的准确性，回收率在 80%至 120%之间。新的分析方法具有出色的重复性和可靠性，可在单次分析运行中精确地定量测定奥美沙坦二甲氧嘧啶片中的 7 种亚硝胺水平。
