Development and validation of a sensitive GC-MS method for the determination of alkylating agent, 4-chloro-1-butanol, in active pharmaceutical ingredients.

The analysis of genotoxic impurities (GTIs) in active pharmaceutical ingredients (APIs) is a challenging task. The target detection limit (DL) in an API is typically around 1 ppm (1 µg/g API). Therefore, a sensitive and selective analytical method is required for their analysis.

Novel sensitive determination method for a genotoxic alkylating agent, 4-chloro-1-butanol, in active pharmaceutical ingredients by LC-ICP-MS employing iodo derivatization.

An alkylating agent, 4-chloro-1-butanol, is a genotoxic impurity (GTI); it may be generated during the synthesis of active pharmaceutical ingredients (APIs). For the trace-level detection of GTIs in APIs, usually, gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) is employed. In this study, a novel LC-inductively coupled plasma (ICP)-MS method was developed and validated.