title: A method for quantitative analysis of an anticancer drug in human plasma with CE-ESI-TOF-MS.
abstract: In this study, the extraction recoveries of an anticancer drug (Imatinib) from human plasma using a common liquid-liquid extraction (LLE) method and a new strong cation exchange (SCX) solid-phase extraction (SPE) column was investigated. The extracts were analyzed with CE coupled on-line to electrospray ionization (ESI) time-of-flight mass spectrometry (TOF-MS) using a monoquaternarized piperazine compound (M7C4I) for capillary coatings. Clean extracts with high and reproducible extraction recoveries ranging between 85 and 91% with % RSD values of 2.5% (n = 3) were obtained using the SCX-SPE columns. This can be compared with the recoveries obtained with the LLE method ranging between 30 and 35%. The CE-ESI-TOF-MS analysis was performed in <10 min with peak efficiencies up to 4.7 × 10⁵ plates/m and an average % RSD for the repeatability of the migration times of the analytes of 1.9% (n = 3) using acidic buffer and adding 5% ACN to the sample. The calibration curves were linear over the range of 0-1500 ng/mL with correlation coefficient (R² ≥ 0.997 and % RSD values of 0.5% (n=3). The intra-day and inter-day assay variations were lower than 8%. The presented CE-ESI-TOF-MS method with the use of SCX-SPE columns yielded rapid, efficient and high extraction recoveries together with high sensitivity (LOD 5 ng/mL), selectivity and good linearity. Accordingly, the method can readily be used for accurate determination and therapeutic monitoring of the Imatinib blood levels for more effective patient treatment. In addition, it can be applied for the extraction, quantification and clinical assessments of metabolites of Imatinib and other basic pharmaceutical drug molecules in biological fluids or pharmaceutical dosage forms.
authors.affiliation: Analytical Chemistry, Department of Physical and Analytical Chemistry, Uppsala University, Uppsala, Sweden. anisa.elhamili@kemi.uu.se
authors.forename: Anisa
authors.initials: A
authors.lastname: Elhamili
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D002412:Cations / Q000737:chemistry; D005591:Chemical Fractionation / Q000379:methods*; D016903:Drug Monitoring; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D007474:Ion Exchange; D016014:Linear Models; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D002412:Cations; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate