A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of cabazitaxel, a novel tubulin-binding taxane, in 100μl aliquots of human lithium heparinized plasma with deuterated cabazitaxel as internal standard. The sample extraction and cleaning-up involved a simple liquid-liquid extraction with 20μl aliquots of 4% ammonium hydroxide, 100μl aliquots of acetonitrile and 1ml aliquots of n-butylchloride. Chromatographic separations were achieved on a reversed phase C 18 column eluted at a flow-rate of 0.20ml/min on a gradient of acetonitrile. The overall cycle time of the method was 5min, with cabazitaxel eluting at 3.0min. The multiple reaction monitoring transitions were set at 836>555 (m/z), and 842>561 (m/z) for cabazitaxel and the internal standard, respectively. The calibration curves were linear over the range of 1.00-100ng/ml with the lower limit of quantitation validated at 1.00ng/ml. The within-run and between-run precisions, also at the level of the LLQ, were within 8.75%, while the accuracy ranged from 88.5 to 94.1%. As dilution of samples prior to extraction resulted in a loss of cabazitaxel of approximately 6.5% per dilution step, a second calibration curve ranging from 40.0 to 4000ng/ml was validated and was also linear. The within-run and between-run precisions in this range were within 4.99%, while the accuracy ranged from 95.8 to 100.3%. The method was successfully applied to samples derived from a clinical study.

Cabazitaxel, Human plasma, LC-MS/MS, Non specific binding, Validated
dx.doi.org/10.1016/j.jpba.2011.10.010, hdl.handle.net/1765/66461
Journal of Pharmaceutical and Biomedical Analysis
Department of Medical Oncology

de Bruijn, P.J, de Graan, A.J.M, Nieuweboer, A.J.M, Mathijssen, A.H.J, Lam, M.H, de Wit, R, … Loos, W.J. (2012). Quantification of cabazitaxel in human plasma by liquid chromatography/triple-quadrupole mass spectrometry: A practical solution for non-specific binding. Journal of Pharmaceutical and Biomedical Analysis, 59(1), 117–122. doi:10.1016/j.jpba.2011.10.010