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

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) u...

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Main Author: Liong, Tan Ka
Format: Thesis
Language:English
Published: 2013
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Online Access:http://eprints.usm.my/60900/1/TAN%20KA%20LIONG%20-%20e.pdf
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spelling my-usm-ep.609002024-11-17T07:05:29Z 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 2013-03 Liong, Tan Ka R Medicine RC254-282 Neoplasms. Tumors. Oncology (including Cancer) RC648-665 Diseases of the endocrine glands. Clinical endocrinology 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. 2013-03 Thesis http://eprints.usm.my/60900/ http://eprints.usm.my/60900/1/TAN%20KA%20LIONG%20-%20e.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution Universiti Sains Malaysia
collection USM Institutional Repository
language English
topic R Medicine
R Medicine
R Medicine
spellingShingle R Medicine
R Medicine
R Medicine
Liong, Tan Ka
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
description 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.
format Thesis
qualification_level Master's degree
author Liong, Tan Ka
author_facet Liong, Tan Ka
author_sort Liong, Tan Ka
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
granting_institution Universiti Sains Malaysia
granting_department Pusat Pengajian Sains Perubatan
publishDate 2013
url http://eprints.usm.my/60900/1/TAN%20KA%20LIONG%20-%20e.pdf
_version_ 1818647358406131712