Журнал хроматографии и методов разделения
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An LC/MS Assay for Analysis of Vorinostat in Rat Serum and Urine: Application to a Pre-Clinical Pharmacokinetic Study

Elham A. Mohamed, Mahasen M. Meshali, Casey L. Sayre, Stephanie E. Martinez, Connie M. Remsberg, Jody K. Takemoto, Thanaa M. Borg, Abdel Monem M. Foda and Neal M. Davies

The utility of currently reported liquid chromatography mass spectrometry methods for quantitation of vorinostat in plasma or serum may be limited. These methods employ time consuming and expensive procedures such as solid phase extraction or limited-access techniques such as high turbulence liquid chromatography coupled with column switching. This study offers a simple isocratic LC/MS method validated for determination of vorinostat in both rat serum and urine. Proteins were precipitated from serum using ice-cold acetonitrile and daidzein was used as internal standard. Separation was achieved using a Phenomenex  Luna ®  C 18  (2) (5 μm, 250 x 4.60 mm) column and isocratic elution with a mobile phase consisting of acetonitrile, water, and formic acid (30:70:0.1, v/v/v). Mass spectrometry detection using electrospray positive-mode ionization with selected ion monitoring detection was employed. The calibration curves were linear ranging from 0.05 to 50 μg/ml in serum and from 0.5 to 25 μg/ml in urine. In both biological matrices, assay precision was <15% (RSD) and the intra- and inter-run bias were within acceptable range (–15% to 15%). No degradation of vorinostat in either matrix was found following three freeze-thaw cycles and 24 h storage in the auto-injector. The lower limit of quantitation in rat serum and urine were 0.05 and 0.5 μg/ml, respectively. The upper limit of quantitation in rat serum and urine were 50 and 25 μg/ml, respectively. This assay was applied successfully to a pre-clinical study of vorinostat pharmacokinetics in rats.