Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (9): 623-629.DOI: 10.5246/jcps.2018.09.064

• Original articles • Previous Articles     Next Articles

Development and validation of a sensitive HPLC method for the determination of lisinopril in human plasma after derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole

Reza Ahmadkhaniha1, Noushin Rastkari2, Syed Husain Hashemi Mousavi3, Effat Souri4*   

  1. 1. Department of Human Ecology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
    2. Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
    3. Department of Chemistry, Faculty of Engineering, South Tehran Branch, Islamic Azad University, Tehran, Iran
    4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Received:2018-04-13 Revised:2018-06-20 Online:2018-09-29 Published:2018-07-11
  • Contact: Tel.: +98-21-66959065; Fax: +98-21-66461178, E-mail:
  • Supported by:

    The part of a Pham D thesis supported by Tehran University of Medical Sciences (Grant No. 23049-92-02-92).


In this study, we developed a simple and sensitive HPLC method for the determination of lisinopril in human plasma. The sample clean-up was carried out by solid-phase extraction (SPE) using a cation-exchange (Strata-SCX®) extraction cartridge. After a pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, the reaction mixture was analyzed on an Agilent Zorbax SB®-C18 (150 mm×4.6 mm, 5 μm). The flow rate was set at 1.0 mL/min. Fluorescence detection was performed at an excitation wavelength of 470 nm and an emission wavelength of 530 nm. The mobile phase consisted of a mixture of methanol and 0.02 M sodium dihydrogen phosphate (pH = 3.0, 60:40, v/v). The average extraction recovery of lisinopril and fluvoxamine (internal standard) was >85%. The method exhibited a linear calibration curve over the concentration range of 11000 ng/mL with a correlation coefficient (r2) of ≥0.98 and a limit of quantification (LOQ) equal to 2 ng/mL. The within-run and between-run precisions were satisfactory with an RSD of 3.8%–13.7% (accuracy: from 95.0% to 96.4%) and 4.273%–14.3% (accuracy: from 94.4% to 98.5%), respectively.

Key words: Lisinopril, HPLC, Derivatization, 4-Fluoro-7-nitro-2,1,3,-benzoxadiazole

CLC Number: