Shifting the linear range of the calibration curves for the quantification of oral molecular-targeted anticancer drugs and the active metabolite in human plasma using LC-ESI-MS/MS

• Published in: Medical Mass Spectrometry Vol. 6; no. 1; pp. 52 - 63
• Main Authors: Hirasawa, Tensei, Masafumi@Kikuchi, 1,2, Takasaki, Shinya, Kumondai, Masaki, Sato, Yu, Sato, Toshihiro, Imoto, Eishi, Hayakawa, Yoshihiro, Maekawa, Masamitsu, Mano, Nariyasu
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society for Biomedical Mass Spectrometry 25.06.2022
• Subjects: collision energy; in-source collision-induced dissociation; LC-ESI-MS/MS; oral kinase inhibitor; simultaneous quantification
• ISSN: 2432-7441; 2432-745X
• DOI: 10.24508/mms.2022.06.006

Many types of oral kinase inhibitors, including imatinib and gefitinib, have become clinically available and have significantly contributed to improving the survival outcomes in cancer patients. Therapeutic drug monitoring of some oral kinase inhibitors is important for ensuring the efficacy and safety of these drugs. Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been used for the simultaneous quantification of these drugs in the human plasma. However, the development of a simultaneous LC-MS/MS analytical method is difficult owing to the differences in mass spectrometry (MS) sensitivity and the therapeutic range of each drug. In this study, we investigated the linear range shifts of calibration curves by adjusting the collision energy defect, in-source collision-induced dissociation, secondary product ion selected reaction monitoring, and isotopologue selected reaction monitoring to develop a simultaneous quantification method for 20 oral kinase inhibitors and active metabolite of sunitinib. Although these four techniques could easily adjust the number of ions introduced to the MS when used individually, it was difficult to adapt 21 analytes using only one technique. Therefore, it is important to utilize multiple techniques, considering the therapeutic concentration range of each drug, in order to develop a method for the simultaneous quantification of oral kinase inhibitors and active metabolites in molecular-targeted therapy.