Validated method using liquid chromatography-electrospray ionization tandem mass spectrometry for the determination of contamination of the exterior surface of vials containing platinum anticancer drugs

Abstract

Contamination of the exterior surface of vials of cytostatic drugs by the drugs themselves is a potential hazard to human health. This study developed a validated method using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the determination of contamination of the exteriors of vials of cisplatin and carboplatin. Large Alpha® sampling swabs were employed to wipe the vial exterior. Cisplatin or carboplatin and gold(III) as an internal standard were derivatized by N,N-diethyldithiocarbamate (DDTC). Pt(DDTC)3+ and Au(DDTC)2+ were monitored by the respective transitions of m/z 639.3–490.9 and 493.0–345.0, respectively. Each separation was completed within 9min using a 3μm particle ODS-column. Calibration curves for cisplatin and carboplatin were linear over concentration ranges of 30–10,000 and 30–30,000pgvial−1, respectively. The accuracies and precisions were 96.1–102.5% and within 8.2% for intra-assay and 99.6–103.3% and within 7.6% for inter-assay, respectively. Their lower limit of quantification was 30pgvial−1. Amounts of 0.17–17.0ngvial−1 as cisplatin and 0.48–794ngvial−1 as carboplatin were detected from the exterior surface of the vials. This validated method using LC-ESI-MS/MS for the determination of platinum anticancer drugs is helpful for monitoring contamination of the exterior surface of drug vials.