Quantitative determination of platinum complexes in human plasma generated from the oral antitumour drug JM216 using directly coupled high-performance liquid chromatography-inductively coupled plasma mass spectrometry without desolvation

Abstract

A new method was developed and validated for measuring platinum species generated from the clinical antitumour agent JM216 in methanol extracts of human plasma using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Good separation of JM216 and three of its biotransformation products (JM118, JM518 and JM383) was achieved with a run time of 20 min using a C8 column (4.6×150 mm) and a gradient methanol-water mobile phase (pH 2.5) at a flow rate of 1 ml min ^–1 . The presence of methanol in the mobile phase and in the sample matrix suppressed the platinum counts and the gradient step was associated with some base-line drift. However, the quantitation of JM216 and its biotransformation products (JM118, JM518 and JM383) was achieved with good intra-assay precision (range 1-12% RSD), inter-assay precision (range 2.3-11% RSD), accuracy (range 89-103%) and limits of quantitation (range 1-2 ng ml ^–1 ) without having to use a desolvation device. This new HPLC-ICP-MS technique has the advantages of greater sensitivity and efficiency compared to existing methods that use HPLC, fraction collection and the off-line detection of platinum by AAS.