SUBSTITUTION REACTIONS IN APCI NEGATIVE MASS SPECTROMETRY: ANALYSIS OF 1-CHLORO-2-NITROBENZENE IN QUETIAPINE FUMARATE

Abstract

A new, sensitive, and rapid UPLC-MS method for the determination of 1-chloro-2-nitrobenzene in ultra performance liquid chromatography mass spectrometry using substitution reactions in atmospheric pressure chemical ionization negative mode [APCI (–)] is described. Substitution reactions [M – X + O]⁻ are observed for compounds which do not easily undergo deprotonation. By using threshold of toxicological concern (TTC), a limit of 1.63 ppm was calculated based on maximum daily dose of the drug substance. The proposed method was found to be linear from 50.0 to 2000.0 ppb with correlation coefficient >0.99. LOD and LOQ of the method were very low as 20.0 and 50.0 ppb. The accuracy of the method was found to be in the range of 85–105%. This method is a good quality control tool for quantification of 1-chloro-2-nitrobenzene at low levels in quetiapine fumarate.

Keywords:

• 1-chloro-2-nitrobenzene
• APCI negative mode
• substitution reactions
• single reaction monitoring (SIR)
• TTC
• UPLC-MS

ACKNOWLEDGMENT

I would like to thank Mr. KK Kuttappa and Mr. James Nadar for laboratory support, Mrs. Neha Deolankar for biblical support, and Waters India for providing analytical instrumentation.