title: 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 9 min using a 3 μm 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 30 pg vial(-1). Amounts of 0.17-17.0 ng vial(-1) as cisplatin and 0.48-794 ng vial(-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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Osawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Naoya
authors.initials: N
authors.lastname: Suzuki
authors.forename: Kimie
authors.initials: K
authors.lastname: Imai
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry; D016190:Carboplatin / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D002945:Cisplatin / Q000032:analysis* / Q000737:chemistry; D004050:Ditiocarb / Q000737:chemistry; D004349:Drug Packaging; D006046:Gold / Q000737:chemistry; D015394:Molecular Structure; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D006046:Gold; D004050:Ditiocarb; D016190:Carboplatin; D002945:Cisplatin