Ultra-high performance liquid chromatography (uhplc) method development and validation for the determination of serum imatinib and its active metabolite concentration among chronic myeloid leukemia patients

Liong, Tan Ka (2013) Ultra-high performance liquid chromatography (uhplc) method development and validation for the determination of serum imatinib and its active metabolite concentration among chronic myeloid leukemia patients. Masters thesis, Universiti Sains Malaysia.

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Abstract

A simple and sensitive method for the simultaneous detection of imatinib mesylate and its active metabolite, N-desmethylimatinib, in human serum samples was developed. Separation was successfully achieved using an Agilent® ZORBAX Eclipse plus Cis reversed phase column (50 x 2.1 mm, i.d.; 1.8 pm) under isocratic mobile phase conditions consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate with 0.2% triethylamine added at pH 3 (25:75, v/v) and ultra-violet detection at 235 nm. Extraction of the target compounds was completed by a protein precipitation method using 100% cold acetonitrile. Good linearities (r2 > 0.99) for Ndesmethyhmafaob and imatinib mesylate were achieved for the concentration ranges of 50-360 ng/mL and 50-1800 ng/mL, respectively. The detection limits were 20 ng/mL and 10 ng/mL for N-desmethylimatinib and imatinib mesylate, respectively. The intra- and inter-day precisions were less than 1% while the percentage recoveries were more than 95%. The method was successfully applied to calculate the pharmacokinetic parameters of chronic myeloid leukemia patients receiving imatinib. For imatinib, mean Vd was 113.32 ± 43.52 L, CL was 5.012 ± 0.028 L and AUC was 62953.33 ± 9791.38 ng.h.L’1. For N-desmethylimatirab, mean Vd was 415.27 ± 228.72 L, CL was 4.84 ± 3.85 L and AUC was 5585.15 ± 2950.42 ng.h.L’1. The method is suitable to be routinely applied for determination of ZV-ctesTnetAyZimatinib and imatinib mesylate in serum.

Item Type: Thesis (Masters)
Uncontrolled Keywords: chronic myeloid leukemia patients
Subjects: R Medicine
R Medicine > RC Internal medicine > RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RC Internal medicine > RC648-665 Diseases of the endocrine glands. Clinical endocrinology
Divisions: Kampus Kesihatan (Health Campus) > Pusat Pengajian Sains Perubatan (School of Medical Sciences) > Thesis
Depositing User: Mr Husnan Budin
Date Deposited: 17 Nov 2024 07:05
Last Modified: 17 Nov 2024 07:05
URI: http://eprints.usm.my/id/eprint/60900

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