The development and clinical validation of a turbulent-flow liquid chromatography–tandem mass spectrometric method for the rapid quantitation of docetaxel in serum

BackgroundDocetaxel is a second generation taxane utilized as an anti-neoplastic agent in cancer chemotherapies. Traditional treatment regimens have resulted in significant adverse effects, resulting in the shift to more frequent drug administration at lower doses. As a result, it is important to monitor serum docetaxel concentrations to optimize efficacy and minimize adverse effects.MethodsSerum containing docetaxel was combined with acetonitrile containing deuterated internal standard, and following protein precipitation, supernatant was diluted with water for on-line sample extraction. Following turbulent-flow chromatography (TFC), analytic separation was achieved on a Hypersil Gold C-18 (50 × 2.1 mm) column and the eluent analyzed using a TSQ Vantage mass spectrometer with selected reaction monitoring. Matrix effects were characterized in addition to carryover, precision, linearity, recovery and functional sensitivity.ResultsThe simple and complex precision for the assay at multiple concentrations was ≤ 6.2%. The assay has functional sensitivity of < 3 ng/ml, and is linear from 8.1 to 1978 ng/ml. Method comparison studies with a reference HPLC–MS/MS method show a slope of 0.84 with a Spearman coefficient of 0.99.ConclusionsBased on the validation metrics, we have generated a sensitive and automated TFC–MS/MS method for docetaxel quantitation in serum.

► Development of a tandem mass spectrometric method for serum docetaxel quantitation.
► Validation of analytical metrics for a quantitative TFC-MS/MS method.
► Comparison work indicate agreement with a reference quantitative docetaxel method.