Quantitative determination of the anticancer prodrug combretastatin A1 phosphate (OXi4503, CA1P), the active CA1 and its glucuronide metabolites in human urine and of CA1 in plasma by HPLC with mass spectrometric detection

[Display omitted] ► Validated methods for the vascular targeted cancer drug combretastatin A1 in human plasma and urine by HPLC–MS. ► Validated methods for the phosphate pro-drug and three glucuronides found in human urine by HPLC–MS. ► Application to the analysis of patient samples following a Phas...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2012-06, Vol.898, p.1-6
Main Authors: Stratford, Michael R.L., Folkes, Lisa K.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - analysis
Antineoplastic Agents - blood
Antineoplastic Agents - chemistry
Antineoplastic Agents - urine
CA1P
Chromatography, High Pressure Liquid - methods
Diphosphates - analysis
Diphosphates - blood
Diphosphates - chemistry
Diphosphates - urine
Drug Stability
Glucuronide metabolites
Glucuronides - analysis
Glucuronides - blood
Glucuronides - chemistry
Glucuronides - urine
HPLC–MS
Humans
Mass Spectrometry
OXi4503
Plasma
Prodrugs - analysis
Prodrugs - metabolism
Reproducibility of Results
Sensitivity and Specificity
Stilbenes - analysis
Stilbenes - blood
Stilbenes - chemistry
Stilbenes - urine
Urine
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Summary:[Display omitted] ► Validated methods for the vascular targeted cancer drug combretastatin A1 in human plasma and urine by HPLC–MS. ► Validated methods for the phosphate pro-drug and three glucuronides found in human urine by HPLC–MS. ► Application to the analysis of patient samples following a Phase I clinical trial of combretastatin A1 phosphate. Validated methods for the determination of CA1, the active agent derived from the prodrug CA1P, in human plasma and urine, and of CA1P and three glucuronides CA1G1, CA1G2 and CA1DG in human urine were developed using LC–MS. Plasma CA1 was extracted using solid phase extraction and validated over the range 5–1000nM. Urine samples were analysed without extraction, and the assays validated over the range 50–2000nM (CA1P), 25–2000nM (CA1), 50–40,000nM (CA1G1 and CA1G2) and 25–4000nM (CA1DG). The mean correlation coefficient (r2) was ≥0.997 for all assays. The intra-day and inter-day accuracy and precision were within the generally accepted criteria for bioanalytical methods (
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2012.03.040