VALIDATION OF A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY-METHOD FOR QUANTIFICATION OF TOTAL VINCRISTINE SULFATE IN HUMAN PLASMA FOLLOWING ADMINISTRATION OF VINCRISTINE SULFATE LIPOSOME INJECTION

The validation of a high performance liquid chromatographic (HPLC) ass ay method for quantitation of total vincristine sulfate (VINC) in huma n plasma is described. VINC was extracted from plasma using BondElut C BA solid phase cartridges with vinblastine as the internal standard. C hromatography was accomplished using a Waters Symmetry C8 (250 mm x 4. 6 mm i.d.) analytical column, a Waters Delta-Pak ODS guard column with a mobile phase of 34.9% water-0.1% diethylamine (pH 7.0)-40% acetonit rile-25% methanol pumped isocratically at 1.0 ml min(-1) with ultravio let detection at 297 nm. Above the limit of quantitation of 28.6 ng ml (-1), the area ratio precision (R.S.D. range 3.33-11.6%) and accuracy of predicted values (R.S.D. range 8.56-23.8% with the limit of quantit ation being the only value above 20%) were acceptable. The assay was l inear from 28.6-2860 ng ml(-1) VINC in plasma. Recovery of VINC from p lasma and VINC from plasma spiked with vincristine sulfate liposome in jection ranged from 74.9-87.1%. Stability of VINC in plasma stored at -20 degrees C for at least 49 days and of extracted plasma samples was demonstrated. Potential interference in quantitation of VINC from com monly co-administered drugs was evaluated along with day-to-day variab ility. The assay procedure was found suitable for evaluation of VINC c linical pharmacokinetics in plasma following administration of vincris tine sulfate liposome injection prepared using distearoylphosphatidylc holine (DSPC)/cholesterol liposomes for injection. (C) 1997 Elsevier S cience B.V.