Background: Enalapril (EPL) is an angiotensin-converting enzyme inhibitor for the treatment of hypertension and chronic heart failure. Enalaprilat (EPLT) is an active metabolite that contributes to the overall activity of EPL. Aim: To quantitate EPL along with its metabolite EPLT using LC–MS/MS, a bioanalytical method was developed and validated with tolbutamide in human plasma using a protein precipitation technique. Results: The sensitive and selective method has an LLOQ of 1 ng/ml with a linearity range of 1–500 ng/ml for both EPL and EPLT using 300 µl of plasma without any matrix effect. Conclusion: Linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples after oral administration of 20 mg of EPL maleate in healthy volunteers demonstrate applicability to bioavailability/bioequivalence studies.

Lay abstract

The present study describes a sensitive, selective, simple, accurate and reproducible LC–MS/MS method for the simultaneous determination of both enalapril (EPL) and enalaprilat (EPLT) in human plasma. The results obtained indicate the high sensitivity of the described method for analysis of EPL and EPLT, which render this method particularly useful for pharmacokinetic or bioequivalence studies. The proposed method has been applied for the analysis of EPL and EPLT in the plasma of healthy volunteers in a single-dose pharmacokinetic study.

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Vol. 3, No. 1

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History

Received 27 September 2016

Accepted 21 November 2016

Published online 2 February 2017

Published in print March 2017

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Acknowledgements

The authors acknowledge the support and the necessary instrumental facilities received from Bioequivalence Study Center, Jadavpur University, India. The authors sincerely acknowledge the editors and the referees for their constructive feedback for improving the quality and raising the clarity of the paper.

Financial & competing interests disclosure

The authors also acknowledges Pharmland JV Leninskaja STR, Nesviz Belarus for providing the necessary gift samples of enalapril maleate. The authors, D Halder and S Dan, are grateful to University Grants Commission (UGC), New Delhi, India for providing the fellowship. 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 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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This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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