Ultra-Sensitive LC-MS/MS Method for the Trace Level Quantification of Six Potential Genotoxic Nitrosamine Impurities in Telmisartan

Nitrosamine impurities are potentially genotoxic which considered under cohort of concern as per ICH M7 guidelines and need to be controlled at trace levels during quantification in drug substances products for safe human consumption. Recent regulatory requirements also suggest the have highly sensitive analytical methods accurate impurities. In this paper we presented simple, rapid ultra-sensitive LC-MS/MS method six potential nitrosamine impurities: N-Nitroso dimethyl amine (NDMA), diethyl (NDEA), Ethyl Iso propylamine (NEIPA), N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) diisopropylamino (NDIPA) dibutyl (NDBA) with a LOQ 0.004 ppm. Chromatographic separation is achieved using Zorbax SB C18 150 × 3.0 mm, 3.5 μ column 0.1% formic water mobile phase A methanol B flow rate 0.3 ml/min gradient mode elution total run time 18 minutes. Six successfully ionized quantified positive atmospheric pressure chemical ionization (APCI) multiple reaction monitoring (MRM). Method validation performed evaluating limit detection found give good S/N ratios linearity range 0.002 - 2 ppm regression coefficient >0.99 all recoveries established three-step sample preparation protocol satisfactory within 80% 120%. The can used routinely applied Nitrosamines Telmisartan concentration 1.5 ng/ml (0.03 respect telmisartan 50 mg/ml).