title: LC-MS-MS determination of imatinib and N-desmethyl imatinib in human plasma.
abstract: A specific and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed for the quantification of imatinib and its primary metabolite N-desmethyl imatinib in human plasma. Protein precipitation with methanol was used for sample preparation. High-performance liquid chromatographic separation was performed on a Thermo BDS Hypersil C18 column (4.6 × 100 mm, 2.4 µm) with methanol-water (55:45, v/v) containing 0.1% formic acid and 0.2% ammonium acetate as the mobile phase, using isocratic elution at a flow rate of 0.7 mL/min. Detection was conducted with positive electrospray ionization multiple reaction monitoring of the ion transitions at m/z 494 → 394 for imatinib, 480 → 394 for N-desmethyl imatinib and 297 → 110 for the internal standard (palonosetron). The assay was validated in the concentration ranges of 8-5,000 ng/mL for imatinib and 3-700 ng/mL for N-desmethyl imatinib. The quantification limits for imatinib and N-desmethyl imatinib were 8 and 3 ng/mL, respectively. The intra-day and inter-day precision values of the assay (expressed as percentage relative standard deviation) were less than 15% at all concentration levels within the tested range, and the accuracy values were between 85 and 115%. The established method was successfully applied to the pharmacokinetic study of imatinib mesylate capsules in 24 healthy Chinese volunteers.
authors.affiliation: 1Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yunjing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuping
authors.initials: S
authors.lastname: Qiang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhongnan
authors.initials: Z
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.forename: Taijun
authors.initials: T
authors.lastname: Hang
mesh_terms: D000328:Adult; D001549:Benzamides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D016014:Linear Models; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate