title: A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of actinomycin-D and vincristine in children with cancer.
abstract: Actinomycin-D (Act-D) and vincristine (VCR) are cytotoxic agents commonly used in the treatment of pediatric cancers. To date, there are few published methods on quantifying Act-D or VCR and no published methods on quantifying the two drugs together. We present a methodology for the simultaneous quantification of Act-D and VCR in human plasma using liquid chromatography-tandem mass spectrometry (LC/MS/MS) detection. Following solid phase extraction, plasma samples were separated and analyzed using electrospray ionization (ESI). The lower limit of quantitation (LLOQ) for both Act-D and VCR was 0.5 ng/ml. The analytical accuracy for detection of both Act-D and VCR was > or = 90%. The analytical precision, as estimated by the coefficient of variation was < or = 6% for Act-D and < or = 11% for VCR. Given the prevalence of the use of the two drugs as combination therapy in a variety of pediatric oncological indications, the small sample volume requirements and the assay sensitivity, this methodology is expected to support several ongoing and future pediatric trials.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Children's Hospital of Philadelphia, Abramson Research Center, Suite 916, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. skolnik@email.chop.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Skolnik
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Heng
authors.initials: H
authors.lastname: Shi
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001800:Blood Specimen Collection; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003609:Dactinomycin / Q000097:blood* / Q000493:pharmacokinetics; D005615:Freezing; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D013058:Mass Spectrometry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013048:Specimen Handling; D014750:Vincristine / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003609:Dactinomycin; D014750:Vincristine