DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD OF N-NITROSODIMETHYLAMINE (NDMA), N-NITROSODIETHYLAMINE (NDEA), N-NITROSOMETHYLAMINOBUTYRIC ACID (NMBA), N-NITROSOETYLISOPROPILAMINE (NEIPA), AND N-NITROSODIISOPROPILAMINE (NDIPA) IMPURITY IN CANDESARTAN CILEXETIL TABLET

• Main Author: Firmana, Triziya
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/69044
• Institution: Institut Teknologi Bandung

Nitrosamines are chemical compounds classified as probable human carcinogens based on animal studies. These angiostensin-receptor blocker medicines have a specific ring structure (tetrazole) whose synthesis could potentially lead to the formation of nitrosamine impurities. An ultra-performance liquid chromatography tandem with mass spectrometry with atmospheric pressure chemical ionization interface has been developed and validated for simultaneous determination of N- nitrosodimethylamine (NDMA), N-hitrosodiethylamine (NDEA), N- nitrosomethylbutyric acid (NMBA), N-nitrosoetylisopropilamine (NEIPA), dan N- nitrosodiisopropilamine (NDIPA) in Candesartan Cilexetil Tablet. NDMA, NDEA, NMBA, NEIPA, and NDIPA were analyzed on L1; 4.6 x 150 mm; 5 µm (Gemini C18) column with the gradient mobile phase with formic acid 0.1% (v/v) and methanol at a flow rate 0.5 mL/minutes. MS parameters were optimized by quality by design (QbD) for critical parameters that impact nitrosamine response. The procedure was fully validated according to ICH Q2 parameters in terms of specificity, linearity, limit of detection, limit of quantification , accuracy, precision, and range and the results meet the acceptance criteria. Validation results proved the procedure is reliable and applicable for analysis of nitrosamine impurities in candesartan cilexetil tablet.