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Determination of anti-cancer drug actinomycin D in human plasma by liquid chromatography-mass spectrometry

Lookup NU author(s): Professor Gareth Veal, Julie Errington, Julieann Sludden, Melanie Griffin, Annie Parry, Dr Juliet Hale, Professor Andrew Pearson, Professor Alan Boddy

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Abstract

Actinomycin D is an anti-cancer drug commonly used in the treatment of paediatric malignancies such as Wilms' tumour, Ewing's sarcoma and rhabdomyosarcoma. Despite its long history of clinical use, little is known about the pharmacokinetics of actinomycin D in humans, largely due to problems in developing an analytical assay with the required sensitivity to measure relevant clinical concentrations. As actinomycin D treatment in children with cancer is associated with veno-occlusive disease (VOD), and as the dose intensity of actinomycin D treatment has been defined as a significant risk factor for the development of this potentially life-threatening hepatic toxicity, pharmacokinetic studies of actinomycin D may be beneficial in optimizing treatment with this drug. In order to investigate this issue, we developed a sensitive liquid chromatography-mass spectrometry (LC-MS) method for the determination of actinomycin D in human plasma samples. Extraction of analytical samples was carried out with acetonitrile and analysis performed on an API 2000 LC/MS/MS using an internal standard of 7-aminoactinomycin D. A limit of quantitation of 1.0ng/ml was determined, allowing the reliable measurement of actinomycin D in plasma samples obtained from patients receiving this drug clinically. The method demonstrated good reproducibility, over the calibration curve range of 1.0-100ng/ml, with intra- and inter-assay precision CVs of 2.7-11.3 and 2.3-7.8%, respectively. Accuracy data showed relative errors of 2.0-16.4 and 10.4-15.2% for intra-assay (n=10) and inter-assay (n=7) experiments, respectively. Initial results of actinomycin D pharmacokinetics in paediatric patients are shown. © 2003 Published by Elsevier B.V.


Publication metadata

Author(s): Veal, G. J., Errington, J., Sludden, J., Griffin, M. J., Price, L., Parry, A. P., Hale, J. P., Pearson, A. D. J., Boddy, A. V.

Publication type: Article

Publication status: Published

Journal: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

Year: 2003

Volume: 795

Issue: 2

Pages: 237-243

Print publication date: 05/10/2003

ISSN (print): 1570-0232

ISSN (electronic): 1873-376X

URL: http://dx.doi.org/10.1016/S1570-0232(03)00573-7

DOI: 10.1016/S1570-0232(03)00573-7

PubMed id: 14522028


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