Development of a Validated UPLC-MS/MS Method for Simultaneous Estimation of Neratinib and Curcumin in Human Plasma: Application to Greenness Assessment and Routine Quantification.

Abstract

A validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the first-ever simultaneous analysis of neratinib, curcumin and internal standard (imatinib) using acetonitrile as the liquid-liquid extraction medium. On a BEH C18 (100mm × 2.1mm, 1.7μm) column, the analytes were separated isocratically using acetonitrile (0.1% formic acid):0.002M ammonium acetate. The flow rate was set at 0.5mL.min-1. The authors utilized multiple reaction monitoring-based transitions for the precursor-to-product ion with m/z 557.099→111.928 for neratinib, m/z 369.231→176.969 curcumin and m/z 494.526→394.141 for imatinib during the study. Validation of the method as per United States Food and Drug Administration requirements for linearity (5-40ngmL-1), accuracy and precision, stability, matrix effect, etc. were investigated and were observed to be acceptable. Afterward, we evaluated the method for establishing its greenness profile by using two greenness assessment tools and found it green. Overall, a reliable green UPLC-MS/MS method was devised and used to estimate neratinib and curcumin in human plasma simultaneously.