Analytical and clinical validation of a dried blood spot assay for the determination of paclitaxel using high-performance liquid chromatography-tandem mass spectrometry

作者：Andriguetti Natalia B; Hahn Roberta Z; Lizot Lilian F; Raymundo Suziane; Costa Jose L; da Cunha Kelly F; Vilela Ramon M M; Kluck Helena M; Schwartsmann Gilberto; Antunes Marina V; Linden Rafael^*

来源：Clinical Biochemistry, 2018, 54: 123-130.

DOI：10.1016/j.clinbiochem.2018.02.020

• Paclitaxel
• Dried blood spots
• Therapeutic drug monitoring
• Liquid chromatography
• Mass spectrometry

Background: Paclitaxel (PCT) is a chemotherapeutic drug widely used for the treatment of several types of tumors, and its use is associated with severe adverse events, mainly neurologic and hematopoietic toxicities. The relation between systemic exposure and clinical response to PCT was previously described, making paclitaxel a potential candidate for therapeutic drug monitoring (TDM). The use of dried blood spot (DBS) sampling could allow complex sampling schedules required for TDM of PCT. The aim of this study was to develop and validate an LC-MS/MS assay for the quantification of PCT in DBS.
Methods: PCT was extracted from one 8 mm DBS punch with a mixture of methanol and acetonitrile, followed by chromatographic separation in a Kinetex C18 (50 x 4.6 mm, 2.6 mu m) column. Detection was performed in a 5500-QTRAP (R) mass spectrometer, with a run time of 2.3 min.
Results: The assay was linear in the range of 2.5 to 400 ng mL(-1). Precision (CV%) and accuracy at the concentration levels of 7.5, 40 and 150 ng mL(-1) were 1.69-4.9% and 106.25 to 109.92%, respectively. PCT was stable for 21 days at 25 and 45 degrees C. The method was applied to DBS samples obtained from 34 patients under PCT chemotherapy. The use of a simple correction factor, derived from the correlation between PCT concentrations in plasma and DBS in this set of patients, allowed unbiased estimation of PCT plasma concentrations from DBS measurements, with similar clinical decisions using either plasma or DBS measurements.
Conclusions: DBS testing of PCT concentrations represents a promising alternative for the dissemination of PCT dose individualization.

• 出版日期2018-4