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Determination of aplidin, a marine-derived anticancer drug, in human plasma, whole blood and urine by liquid chromatography with electrospray ionisation tandem mass spectrometric detection.
- Source :
-
Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2004 Feb 18; Vol. 34 (3), pp. 619-30. - Publication Year :
- 2004
-
Abstract
- A sensitive and highly specific liquid chromatographic method with electrospray ionisation tandem mass spectrometric detection (LC-ESI-MS/MS) is reported for the determination in human plasma, whole blood and urine of Aplidin (APL), a novel depsipeptide derived from the tunicate Aplidium albicans with a potent cytotoxic activity under investigation in clinical studies. Didemnin B was used as internal standard and, after protein precipitation with acetonitrile and liquid-liquid extraction with chloroform, APL was separated by liquid chromatography using a reversed-phase C18 column and a linear gradient of acetonitrile in water (both containing 0.5% formic acid). Detection was performed using a turboionspray source operated in positive ion mode and by multiple reaction monitoring (MRM; m/z 1111 --> 295 for APL and m/z 1113 --> 297 for didemnin B). The method was linear (r > or = 0.9933) over the range 1-250 ng/ml, with intra- and inter-batch precision and accuracy below 12.2% (except at LLOQ < or = 15.4%) for both plasma and urine. Recoveries were moderate, ranging from 54 to 70% in plasma and blood, and from 46 to 60% in urine, for both APL and didemnin B. The LOD was 0.25 ng/ml for both matrices. APL resulted stable in the different matrices at least for 6 h (both at room temperature and 37 degrees C), after freeze and thaw cycles and long term storage at -20 degrees C. The method allowed demonstrating that APL is in a dynamic equilibrium between plasma and blood cells. Moreover, the method was successfully applied to the pharmacokinetic study of Aplidin in cancer patients.
Details
- Language :
- English
- ISSN :
- 0731-7085
- Volume :
- 34
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Publication Type :
- Academic Journal
- Accession number :
- 15127818
- Full Text :
- https://doi.org/10.1016/s0731-7085(03)00557-0