Determination of NDSRI in Chlorpromazine Tablets by LCMS-8050

User Benefits

- Accurate quantification of the sample can be completed in just 5.5 minutes. - The linear minimum concentration is 0.1 ng/mL, which meets the requirement for high sensitivity of the instrument to detect low-limit impurities.

Introduction

Chlorpromazine, a phenothiazine derivative, acts as an antagonist at dopamine, histamine, and cholinergic receptors. Its hydrochloride salt is clinically used to treat psychosis, emesis, hypothermic anesthesia, and artificial hibernation. Due to its tertiary amine structure, chlorpromazine may form nitrosamine impurities (NDSRIs) such as N-Nitroso-desmethyl-chlorpromazine during manufacturing. These impurities are potentially carcinogenic/mutagenic and have prompted drug recalls. FDA classifies N-Nitroso-desmethyl-chlorpromazine as a high-risk Class I nitrosamine, with an Acceptable Intake (AI) limit of 26.5 ng/day. For a maximum daily dose of 600 mg, this corresponds to a limit of 1.1 ng per 25 mg tablet. This study developed an analytical method using LC-MS/MS (Shimadzu LCMS-8050) to quantify N-Nitroso-desmethyl-chlorpromazine in chlorpromazine tablets. The validated method enables accurate and rapid determination of this impurity, providing a reliable approach for quality control.

November 9, 2025 GMT