Simple and rapid determination of carboplatin in plasma by highperformanceliquid chromatography. Error pattern and application to clinical pharmacokinetic studies

Carboplatin is an antitumor agent widely employed in cancer chemotherapy. A specific and selective method for the determination of carboplatin in huma n plasma and its applications to pharmacokinetic investigations is describe d. One ultrafiltration step, through a Centrifree micropartition system (Am icon) at 2000 g for 10 min, is the only requirement as sample treatment. Th e resulting solution is injected into an Inertsil ODS-2 (5 mum, 25 cm X 4.6 mm I.D.) analytical column. The mobile phase consisted of 0.1 M potassium dihydrogenphosphate with 1 mM dipotassium. edetate adjusted to a pH between 3 and 3.5. The limit of quantitation was 1 mg/l. The method showed good re covery (100.68 +/- 5.49%) and precision: the within-day relative standard d eviation (RSD) for carboplatin (3-350 mg/l) was 2.07% and the between-day R SD for carboplatin, in the previously described range, was 1.31%. We determ ined the assay error pattern for proper weighting of serum level data in ph armacokinetic models. The selectivity (discrimination between the parent dr ug arid platinum-containing species such as carboplatin metabolites), simpl icity and speed of this assay for free carboplatin quantitation should faci litate pharmacokinetic investigations and therapeutic drug monitoring. (C) 2001 Elsevier Science BY All rights reserved.