title: Quantification of cabazitaxel in human plasma by liquid chromatography/triple-quadrupole mass spectrometry: a practical solution for non-specific binding.
abstract: 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 100 μl 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 20 μl aliquots of 4% ammonium hydroxide, 100 μl aliquots of acetonitrile and 1 ml aliquots of n-butylchloride. Chromatographic separations were achieved on a reversed phase C₁₈ column eluted at a flow-rate of 0.20 ml/min on a gradient of acetonitrile. The overall cycle time of the method was 5 min, with cabazitaxel eluting at 3.0 min. 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 1.00-100 ng/ml with the lower limit of quantitation validated at 1.00 ng/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 4000 ng/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.
authors.affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, University Medical Center, Rotterdam, The Netherlands. p.debruijn@erasmusmc.nl
authors.forename: Peter
authors.initials: P
authors.lastname: de Bruijn
authors.forename: Anne-Joy M
authors.initials: AJ
authors.lastname: de Graan
authors.forename: Annemieke
authors.initials: A
authors.lastname: Nieuweboer
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: Mei-Ho
authors.initials: MH
authors.lastname: Lam
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Loos
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006801:Humans; D007262:Infusions, Intravenous; D057230:Limit of Detection; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; C552428:cabazitaxel