A Simple and Sensitive LC-MS/MS Method for Simultaneous Quantification of Dasatinib and Erythromycin in Mice Plasma: Application to Preclinical Pharmacokinetic Study.

Abstract

Dasatinib (DAS) is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML) and erythromycin (ERY) is macrolide antibiotic used to treat a range of inflammatory conditions are often co-administered in clinical practice. The simultaneous estimation of DAS and ERY helps in understanding the pharmacokinetics and drug-drug interactions. In this respect, we presented novel, sensitive, and validated bio-analytical LC-ESI-MS/MS method for simultaneous estimation of DAS and ERY in CD-1 mice plasma. The LLOQ was 2.0 ng/mL with an S/N ratio of 15. This validated method was used to study the PK of DAS and ERY in mice following intravenous and oral administration. The DAS was administered at 5 mg/kg via both oral and intraveneous route, whereas ERY was administered at 50 mg/kg orally and 5 mg/kg intraveneousaly. Following intravenous dosing, DAS showed high clearance and distribution, while ERY exhibited high clearance and distribution. The oral bioavailability was 64% for DAS and 21% for ERY. When co-administered orally at 5 mg/kg for DAS and 50 mg/kg of ERY, the AUC and C_max of DAS were unchanged. However, the systemic exposure (w.r.t AUC and C_max) of ERY was slightly higher (2.4-fold) in the presence of DAS, which may be attributed because of the CYP3A4 inhibition potential.