Quantification of orelabrutinib in human plasma and cerebrospinal fluid by liquid chromatography tandem mass spectrometry

A sensitive and simple method was developed to determine orelabrutinib in human plasma and cerebrospinal fluid by liquid chromatography tandem mass spectrometry (LC-MS/MS). The samples were prepared by simple protein precipitation with by 0.1% formic acid acetonitrile solution and efficient separations were performed on the Thermo Hypersll GOLD C18 column (2.1 mm × 150 mm, 5 μm) under a gradient program in a total run time of 9 min. The orelabrutinib was detected by electrospray ionization in positive ion mode with selective reaction monitoring (SRM) and mass spectrometric conditions were optimized in order to increase selectivity and sensitivity. The developed method was validated in terms of its accuracy, precision, selectivity, linearity, recovery, matrix effect, stability, and limits of quantification (LOQ). The lower limit of quantification is 0.50 ng/mL, the intraday and interday precision RSD are both less than 15%, and the recovery rate is 85.7%-92.9%. Finally, the method was successfully applied for the quantitation of orelabrutinib in human plasma and cerebrospinal fluid of clinical patients treated with orelabrutinib.