Pharmacokinetic study of granisetron in human plasma measured by UPLC-MS/MS and its use in healthy Chinese subjects.

Abstract

In this study, a rapid, simple and sensitive UPLC-MS/MS method was established for the quantification of granisetron in human plasma for the prevention of vomiting after radiotherapy and chemotherapy. The precipitated proteins were extracted and gradient eluted on a ZORBAX Eclipse Plus C18 column (2.1×50mm, 1.8μm) to achieve ideal chromatographic separation. Multiple reaction mode (MRM) was performed using a Turboion Spray API5500 mass spectrometer equipped with Electron Spray Ionization (ESI). For method validation, good linearity was observed for each analyte of interest in the validation concentration range of 0.05 to 20.0ng/mL. The CV% of inter-batch and intra-batch precision were in the range of -3.6% to 4.7% and the precision of both inter-batch and intra-batch was ≤15.0%. In addition, the method had the advantage of a low matrix effect. In human plasma, all analytes remained stable for 2 hours when kept at room temperature; samples were stable within the autosampler (5^°C) for 141 h after preparation and after four freeze-thaw cycles at -20^°C and -70^°C for 48 days. The UPLC-MS method that had been validated was later utilized for the pharmacokinetic investigation of granisetron hydrochloride tablets in orally administered doses to healthy Chinese volunteers, both before and after meals.