Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats

Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP(R) MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 x 4.6 mm, 5 mu m). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10-5000 ng/mL (r(2) > 0.99) and 10-2500 ng/mL (r(2) > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.

Automated summary

In this study, a specific, sensitive, and reproducible LC-MS/MS method was developed and validated for the quantification of oxaliplatin (OXP) in rat plasma and tongue tissue. The method showed good linearity, precision, and accuracy. It was successfully used in pharmacokinetic studies and tissue distribution analysis.