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-1β-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 μg/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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Vol. 12, No. 21

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History

Received 19 August 2020

Accepted 28 September 2020

Published online 16 October 2020

Published in print November 2020

Information

Keywords

Acknowledgments

The authors give special thanks to the PTC Chemistry team for providing the stable labeled reference standards of ataluren and ataluren acyl glucuronide.

Financial & competing interests disclosure

The study was sponsored by PTC Therapeutics. The authors are current employees of PTC Therapeutics and may hold stock or other equity positions with the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval for all clinical trial research, which were conducted in accordance with the International Council on Harmonisation (ICH) GCP guidance documents. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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