Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Automated Chemical Laboratories, Royal Scientific Society, Amman 11941, Jordan.
J Chromatogr Sci. 2024 Apr 23;62(4):372-379. doi: 10.1093/chromsci/bmad068.
N-nitrosamine pollutants are probable carcinogens. Regulatory agencies declared their presence in the drugs unsafe for human consumption and demanded their recall. Using ultra-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (UPLC-APCI-MS/MS) in tablet dosage form based on International Conference on Harmonization (ICH) tripartite guideline criteria, we aim to develop and test a new approach for identifying and validating nitrosamine-contaminants, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in irbesartan, olmesartan and metformin. The column was Phenomenex Luna-C18, 100 × 3.0 mm and 3.0 μm. A mobile gradient phase of formic acid in either water or methanol separated the impurities. NDMA and NDEA had retention times of 0.85 and 2.55 min, respectively. The detector's linearity was established at concentrations ranging from 0.6 to 100 ng/mL. R2 for NDMA and NDEA were 0.9996 and 0.9998, respectively, with a linear response function established at 0.6-100 ng/mL. Limit of detection and limit of quantification for NDMA and NDEA were 0.35, 0.29 and 0.55, 0.37 ng/mL, respectively. On average, recovery rates for NDMA and NDEA ranged from 96.0 to 98.4 and 96.2 to 98.0%, respectively. The relative standard deviation for NDMA and NDEA was 3.46 and 2.69, respectively. According to the ICH guidelines, the developed method was quick, sensitive and valid. The pharmaceutical formulations of irbesartan, olmesartan and metformin may be regularly examined using the approach provided here.
亚硝胺污染物可能是致癌物质。监管机构宣布这些药物中存在的亚硝胺对人体食用不安全，并要求召回这些药物。本研究旨在根据国际人用药品注册技术协调会（ICH）三方指导原则标准，采用超高效液相色谱-大气压化学电离串联质谱法（UPLC-APCI-MS/MS），建立并验证一种新方法，用于检测和确证厄贝沙坦、奥美沙坦和盐酸二甲双胍中存在的亚硝胺污染物，即 N-亚硝基二甲胺（NDMA）和 N-亚硝基二乙胺（NDEA）。色谱柱为 Phenomenex Luna-C18，100×3.0mm，3.0μm。流动相为甲酸水或甲酸甲醇溶液，实现杂质分离。NDMA 和 NDEA 的保留时间分别为 0.85 和 2.55min。在 0.6-100ng/mL 浓度范围内，NDMA 和 NDEA 的检测器线性关系良好，相关系数（R2）分别为 0.9996 和 0.9998。NDMA 和 NDEA 的检测限和定量限分别为 0.35、0.29ng/mL 和 0.55、0.37ng/mL。NDMA 和 NDEA 的平均回收率范围分别为 96.0-98.4%和 96.2-98.0%。NDMA 和 NDEA 的相对标准偏差分别为 3.46%和 2.69%。根据 ICH 指南，所建立的方法快速、灵敏、有效。厄贝沙坦、奥美沙坦和盐酸二甲双胍的药物制剂可以采用本文提供的方法定期进行检测。
