Novel LC–MS Method development and Validation for Characterization of Talazoparib, an Anti-cancer drug and its forced degradation behavior

Abstract

The present work aimed to develop a novel liquid chromatography and mass spectrometry (LC-MS) method for the determination of Talazoparib (TZPB) in pharmaceutical forms. Analysis of TZPB was performed in mobile phase of Methanol, Acetonitrile and 0.2% Perchloric acid in the ratio of 70:28:02 (v/v) as mobile phase and separation was carried on Prontosil ODS C18 Column (150 X 4.6mm, 5μ) as stationary phase. The degradative property of the TZPB under different stress conditions were evaluated using mass spectral analysis of the eluted compounds. The characterization of column eluents was carried on mass spectrometer operated in a positive ESI (electrospray ionization) mode and analyzed in single quadrupole analyzer. The mass spectra corresponding to molecular weight of TZPB was observed at m/z of 381 and characteristic mass fragmentation was observed in the spectra (m/z of 339 to 204). The linear calibration curve for TZPB was achieved in the range of 0.1–150 ng/mL (r = 0.9994) with a very sensitive detection limit (0.03ng/mL) and quantification limit (0.1ng/mL). The method was validated for parameters such as accuracy, precision, ruggedness, robustness etc and the results of the validation parameters are within acceptable limit at all quality control levels. The forced degradation studied for conditions such as acid, base, oxidation, UV light and thermal degradation conditions. The method can separate and detect the degradation compounds formed during the stress study. The forced degradation compounds formed were characterized using mass spectral study and a total 9 different degradation compounds were identified in the study. Hence the method can apply in identification and quantification of degradation compounds of TZPB in quality control and formulations.