LC-MS/MS quantification of ataluren and ataluren acyl glucuronide in human plasma/urine: application in clinical studies

被引：0

作者：

Kaushik, Diksha ^{[1
]}

Ma, Jiyuan ^{[1
]}

Gu, Guodong ^{[1
]}

Hwang, Seongwoo ^{[1
]}

Moon, Young-Choon ^{[1
]}

Kong, Ronald ^{[1
]}

机构：

[1] PTC Therapeut, South Plainfield, NJ 07080 USA

来源：

BIOANALYSIS | 2020年 / 12卷 / 21期

关键词：

ataluren; glucuronide metabolites; human plasma; human urine; LC-MS; MS; method validation; quantification;

D O I：

10.4155/bio-2020-0214

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Background:This paper describes for the first-time analytical procedures established to resolve the challenges associated with simultaneous and direct quantification of ataluren and ataluren-O-1 beta-acyl glucuronide (AAG) by LC-MS/MS in human plasma and urine matrices.Methodology/results:The plasma quantification method was validated for calibration range of 12.5-12500 ng/ml for ataluren and 6.25-2500 ng/ml for AAG. The urine quantification method was validated for calibration range of 0.01-10 and 1-1000 mu g/ml for ataluren and AAG, respectively. Plasma and urine samples were stabilized upon collection and through storage to prevent hydrolysis and acyl migration of AAG.Conclusion:Methods described in this paper enabled successful completion of ataluren clinical pharmacology studies for simultaneous pharmacokinetic assessment of ataluren and AAG.

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页码：1545 / 1555

页数：11

相关论文

共 15 条

[1]

E. Agency, 2012, Emerg. Med. Australasia (EMA), V35, P1

[2] Phase 2a Study of Ataluren-Mediated Dystrophin Production in Patients with Nonsense Mutation Duchenne Muscular Dystrophy [J].

Finkel, Richard S. ;

Flanigan, Kevin M. ;

Wong, Brenda ;

Boennemann, Carsten ;

Sampson, Jacinda ;

Sweeney, H. Lee ;

Reha, Allen ;

Northcutt, Valerie J. ;

Elfring, Gary ;

Barth, Jay ;

Peltz, Stuart W. .

PLOS ONE, 2013, 8 (12)

[3] Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy [J].

Kayali, Refik ;

Ku, Jin-Mo ;

Khitrov, Gregory ;

Jung, Michael E. ;

Prikhodko, Olga ;

Bertoni, Carmen .

HUMAN MOLECULAR GENETICS, 2012, 21 (18) :4007-4020

[4] In vitro metabolism, reaction phenotyping, enzyme kinetics, CYP inhibition and induction potential of ataluren [J].

Kong, Ronald ;

Ma, Jiyuan ;

Hwang, Seongwoo ;

Moon, Young-Choon ;

Welch, Ellen M. ;

Weetall, Marla ;

Colacino, Joseph M. ;

Almstead, Neil ;

Babiak, John ;

Goodwin, Elizabeth .

PHARMACOLOGY RESEARCH & PERSPECTIVES, 2020, 8 (02)

[5] Metabolism and Disposition of Ataluren after Oral Administration to Mice, Rats, Dogs, and Humans [J].

Kong, Ronald ;

Ma, Jiyuan ;

Hwang, Seongwoo ;

Goodwin, Elizabeth ;

Northcutt, Valerie ;

Babiak, John ;

Almstead, Neil G. ;

McIntosh, Joseph .

DRUG METABOLISM AND DISPOSITION, 2020, 48 (04) :317-325

[6] Interference of a carbamoyl glucuronide metabolite in quantitative liquid chromatography/tandem mass spectrometry [J].

Liu, DQ ;

Pereira, T .

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2002, 16 (02) :142-146

[7] Ataluren as an Agent for Therapeutic Nonsense Suppression [J].

Peltz, Stuart W. ;

Morsy, Manal ;

Welch, Ellen M. ;

Jacobson, Allan .

ANNUAL REVIEW OF MEDICINE, VOL 64, 2013, 64 :407-425

[8] Nonsense suppression activity of PTC124 (ataluren) [J].

Peltz, Stuart W. ;

Welch, Ellen M. ;

Jacobson, Allan ;

Trotta, Christopher R. ;

Naryshkin, Nikolai ;

Sweeney, H. Lee ;

Bedwell, David M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (25) :E64-E64

[9] Acyl glucuronide drug metabolites: Toxicological and analytical implications [J].

Shipkova, M ;

Armstrong, VW ;

Oellerich, M ;

Wieland, E .

THERAPEUTIC DRUG MONITORING, 2003, 25 (01) :1-16

[10] Acyl glucuronides: Biological activity, chemical reactivity, and chemical synthesis [J].

Stachulski, Andrew V. ;

Harding, John R. ;

Lindon, John C. ;

Maggs, James L. ;

Park, B. Kevin ;

Wilson, Ian D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (24) :6931-6945