Development, Quantification and Validation of a HPLC-UV Method for Analysis of N-Nitroso Aryl Piperazine Quetiapine Impurity in Quetiapine Crude to better control in Final Drug Substance

The Term Nitrosamine describes the class of compounds having structure of Nitroso group bonded to the amine (R¹N (-R²)-N=O. Nitrosamine are probable or possible human carcinogen as classified by International Agency for Research and Cancer (IARC). Nitrosamines can be produced when a secondary amine, tertiary amine or quaternary amine is present with a nitrating source – such as a nitrite, nitrosyl, or nitrate. Any manufacturing process that brings a nitric oxide (NO) source in contact with an amine under these conditions has the potential to produce nitrosamines as a by-product during the manufacturing process, which can be converted to nitrosamines in subsequent synthesis steps if not properly removed. A variety of conditions can drive the reaction like acidity, the presence of reducing agents, or high temperatures. Besides Listed Nitrosamines impurities such as NDMA, NDEA, NMPA, NDIPA, NIPEA, NDBA and NMBA etc. an API molecule or its degradant, process impurities itself having secondary amine, tertiary amine or quaternary amine in its structure is itself a probable source to form N- Nitrosamine derivative which is equally potent and need to be controlled. Thus Nitrosamines impurity profiling is an important aspect in drug therapy for its safety. Hence a simple and accurate method has been developed for quantification and validation of N-Nitroso aryl Piperazine quetiapine impurity in Quetiapine by using High Performance Liquid Chromatography -Ultra Violet (HPLC-UV) system The impurities were analysed on YMC Trait C8 Column(150 mm x 4.6 mm,5 u,120 ° ) analytical column using ternary mixture ammonium acetate buffer pH 9.0: Acetonitrile: Methanol in gradient ratio at the flow of 1.0 mL /min with a run time as per gradient. The method was developed for acceptance criteria of 0.177 ppm of N-Nitroso aryl Piperazine quetiapine in Quetiapine.