Analytical and Bioanalytical Chemistry

, Volume 409, Issue 26, pp 6141–6148 | Cite as

A new LC-MS/MS bioanalytical method for perindopril and perindoprilat in human plasma and milk

  • Ei Mon Phyo Lwin
  • Cobus Gerber
  • Yunmei Song
  • Catherine Leggett
  • Usha Ritchie
  • Sean Turner
  • Sanjay GargEmail author
Research Paper


A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1–200 ng/mL (r 2 = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80–110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and −80 °C.


Perindopril Perindoprilat LC-MS/MS Human plasma Human breast milk Lactation 



I would like to acknowledge the patient and clinicians at Women’s and Children’s Hospital, Adelaide, for supplying patient samples and blank human milk, Australian Red Cross for supplying blank human plasma, and Benjamin Tscharke and Ben Noll for their technical help.

Compliance with ethical standards

Conflict of interest

This authors declare that there is no conflict of interest regarding the publication of this paper. The study was approved by the Women’s and Children’s Hospital Research Ethics Committee (HREC14/WCHN/115) and University of South Australia Research Ethics Committee (0000033979). Written informed consent was obtained from all participants.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Supplementary material

216_2017_552_MOESM1_ESM.pdf (200 kb)
ESM 1 (PDF 199 kb).


  1. 1.
    Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 9th ed. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer business; 2011.Google Scholar
  2. 2.
    Hale TW. Medications and mothers' milk. 15th ed. A manual of lactational pharmacology. USA: Hale Publishing, L.P; 2012.Google Scholar
  3. 3.
    Schaefer C, Peters P, Miller RK. Drugs during pregnancy and lactation. 2nd ed. USA: Elsevier; 2007.Google Scholar
  4. 4.
    Hale TW, Rowe HE. Medications & mothers' milk. 16th ed. The United States of America: Hale Publishing, L.P; 2014.Google Scholar
  5. 5.
  6. 6.
    Coversyl (Perindopril Arginine) - Product Information. Therapeutic Goods Administration, Department of Health, Australian Government; 2012. p. 1-18.Google Scholar
  7. 7.
    Hurst M, Jarvis B. Perindopril. Springer 2001;61(6):867–96.Google Scholar
  8. 8.
    Nordeng H, Havnen GC, Spigset O. Drug use in breastfeeding. Review Article 2012;9(132):1089–93.Google Scholar
  9. 9.
    Hale TW, Rowe HE. Medications & mothers' milk. 17th ed. New York: Springer, LLC; 2017.Google Scholar
  10. 10.
    British Pharmacopoeia (Ph. Eur. monograph 2019). Perindopril Erbumine. 2017.Google Scholar
  11. 11.
    Jain DS, Subbaiah G, Sanyal M, Pande UC, Shrivastav P. First LC-MS/MS electrospray ionization validated method for the quantification of perindopril and its metabolite perindoprilat in human plasma and its application to equivalence study. J Chromatogr. 2006;837:92–100.Google Scholar
  12. 12.
    Nirogi RV, Kandikere VN, Shukla M, Mudigonda K, Maurya S, Komarneni P. High-throughput quantification of perindopril in human plasma by liquid chromatography/tandem mass spectrometry: application to a bioequivalence study. Rapid Commun Mass Spectrom. 2006;20(12):1864–70.CrossRefGoogle Scholar
  13. 13.
    Biopharmaceutics. Guidance for Industry: Bioanalytical Method Validation (Draft). USA: U.S. Department of Health and Human Servuces, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM); 2013.Google Scholar
  14. 14.
    Lwin EMP, Gerber C, Song Y, Leggett C, Ritchie U, Turner S, et al. A new LC-MS/MS bioanalytical method for atenolol in human plasma and milk. Bioanalysis. 2017;9(7):517-30.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Ei Mon Phyo Lwin
    • 1
  • Cobus Gerber
    • 1
  • Yunmei Song
    • 1
  • Catherine Leggett
    • 2
  • Usha Ritchie
    • 2
  • Sean Turner
    • 2
  • Sanjay Garg
    • 1
    Email author
  1. 1.School of Pharmacy and Medical SciencesUniversity of South AustraliaAdelaideAustralia
  2. 2.SA PharmacyWomen’s and Children’s HospitalAdelaideAustralia

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