title: Method development and validation for the simultaneous determination of imatinib mesylate and N-desmethyl imatinib using rapid resolution high performance liquid chromatography coupled with UV-detection.
abstract: We developed a simple and sensitive method for the simultaneous detection of imatinib mesylate (IM) and its active metabolite, N-desmethyl imatinib (M1), in human serum samples. Separation was successfully achieved using an Agilent(®) ZORBAX Eclipse plus C(18) reversed phase column (50 mm × 2.1 mm, i.d.; 1.8 μm) under isocratic mobile phase conditions consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate with 0.2% triethylamine at pH 3 (25:75, v/v) and ultra-violet detection was achieved at 235 nm. Extraction of the target compounds was completed using 100% cold acetonitrile. Good linearities (r(2)>0.99) for both IM and M1 were achieved for the concentration ranges of 50-1800 ng/mL and 50-360 ng/mL, respectively. The detection limits were 20 ng/mL and 10 ng/mL for M1 and IM, respectively. The intra- and inter-day precisions were less than 1% with percent recoveries of more than 90%. The method was successfully applied to calculate the pharmacokinetic parameters of chronic myeloid leukemia patients receiving imatinib. The method is suitable to be routinely applied for determination of IM and M1 in serum.
authors: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors: Ka Liong
authors: KL
authors: Tan
authors: Ravindran
authors: R
authors: Ankathil
authors: Siew Hua
authors: SH
authors: Gan
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000068877:Imatinib Mesylate; D016018:Least-Squares Analysis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate