title: A sensitive and selective liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of actinomycin-D and vincristine in children with cancer.
abstract: We describe a selective and a highly sensitive assay for actinomycin-D (Act-D) and vincristine (VCR) in plasma employing high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection. The intraday precision (as defined by the coefficient of variation, CV) based on the standard deviation of replicates of quality control samples ranged from 4.9 to 7.5% and 6.5 to 11.3% with accuracy ranging from 90.7 to 98.1% and 91.2 to 103% for Act-D and VCR, respectively. The interday precision ranged from 7.2 to 10.0% and 11.3 to 13.0% and the accuracy ranged from 94.3 to 102% and 90.7 to 91.6% for Act-D and VCR, respectively. Stability studies showed that Act-D and VCR were stable both during the assay procedure and long-term storage. The lower limit of quantitation (LLOQ) for both Act-D and VCR was 0.05 ng/ml. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully employed in a pharmacokinetic study of these agents in children with cancer, and is expected to support several ongoing and future pediatric trials.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Lee
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Skolnik
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003609:Dactinomycin / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D014750:Vincristine / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000903:Antibiotics, Antineoplastic; D003609:Dactinomycin; D014750:Vincristine