Determination of CC-5013, an analogue of thalidomide, in human plasma by liquid chromatography-mass spectrometry.
A high-performance liquid chromatographic assay with MS detection has been developed for the quantitative determination of the anti-angiogenic agent CC-5013 in human plasma. Sample pretreatment involved liquid-liquid extraction with acetonitrile/1-chlorobutane (4:1, v/v) solution containing the internal standard, umbelliferone. Separation of the compounds of interest was achieved on a column packed with Waters C18 Nova-Pak material (4 microm particle size; 300 mm x 3.9 mm internal diameter) using acetonitrile, de-ionized water, and glacial acetic acid in ratios of 20:80:0.1 (v/v/v) (pH 3.5) delivered at an isocratic flow rate of 1.00 ml/min. Simultaneous MS detection was performed at m/z 260.3 (CC-5013) and m/z 163.1 (umbelliferone). The calibration curve was fit to a linear response-concentration data over a range of 5-1000 ng/ml using a weighting factor of 1/x. Values for accuracy and precision, obtained from four quality controls analyzed on three different days in replicates of five, ranged from 98 to 106% and from 5.5 to 15.5%, respectively. The method was successfully applied to study the pharmacokinetics of CC-5013 in a cancer patient receiving the drug as single daily dose.
Tohnya
Tanyifor M
TM
Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA.
Hwang
Kyunghwa
K
Lepper
Erin R
ER
Fine
Howard A
HA
Dahut
William L
WL
Venitz
Jürgen
J
Sparreboom
Alex
A
Figg
William D
WD
D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000077269:Lenalidomide; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics
D013792:Thalidomide; D000077269:Lenalidomide