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

Mark A. Marzinke, Autumn R. Breaud, William Clarke

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Docetaxel 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. Methods: Serum 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. Results: The 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. Conclusions: Based on the validation metrics, we have generated a sensitive and automated TFC-MS/MS method for docetaxel quantitation in serum.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalClinica Chimica Acta
Volume417
DOIs
StatePublished - Feb 8 2013

Keywords

  • Assay validation
  • Docetaxel
  • LC-MS/MS
  • Turbulent-flow chromatography

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

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