Development and Validation of LC--MS Method for the Determination of Lisinopril in Human Plasma and its Application in a Bioequivalence Study

Abstract

A rapid, simple, and specific liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method has been developed and validated for the determination of lisinopril in human plasma. Enalaprilat was used as the internal standard (IS). Sample preparation of the serum involved deproteination with methanol twice, repeatedly. Samples were separated using a Thermo Hypersil-HyPURITY C18 reversed-phase column (150 x 2.1 mm i.d., 5 microm). Mobile phase consisted of formic acid solution (pH 2.9)-methanol-acetonitrile (58:25:17, v/v). Lisinopril and its internal standard were measured by electrospray ion source in positive selected ion monitoring mode. The method was validated with a linear range of 2.5-320 ng/mL and the lowest limits of quantitation were 2.5 ng/mL for lisinopril. The extraction efficiencies were approximately 80% and recoveries of method were in range of 94.4-98.2%. The intra-day relative standard deviation (RSD) was less than 8.8% and inter-day RSD was within 10.3%. QC samples were stable when kept at ambient temperature for 24 h, at -20 degrees C for 30 days and after four freeze/thaw cycles. The method has been successfully applied to the evaluation of pharmacokinetics and bioequivalence of 2 lisinopril formulations in 18 healthy Chinese volunteers after an oral dose of 20 mg.

Quantitative determination of lisinopril in human plasma by high performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

“…Typical equations for the calibration curves were: y = 1.32 × 10 −2 x + 1.35 × 10 −3 , r = 0.998. The LLOQ for lisinopril was 1.03 ng/mL in plasma, which was lower than the values reported in the literature (Kousoulos et al , ; Padua et al , ; Qin et al , ; Tashtoush et al , ; Tsakalof et al , ; Zhou et al , ).…”

“…Finally, a mobile phase consisting of methanol–water containing 0.2% formic acid (55:45, v/v) was used. Under the optimal conditions, the total run time for each sample was only 2.5 min, which was shorter than the values (3.5–10 min) reported for HPLC/MS methods in the literature (Huang et al , ; Padua et al , ; Qin et al , ; Tashtoush et al , ; Tsakalof et al , ; Zhou et al , ).…”

“…This paper describes an improved, rapid, selective and sensitive HPLC‐MS/MS method that enables the determination of lisinopril with good accuracy at low drug concentrations in human plasma. The lower limit of quantification (LLOQ) was 1.03 ng/mL, which was lower than that reported in the literature (Kousoulos et al , ; Padua et al , ; Qin et al , ; Tashtoush et al , ; Tsakalof et al , ; Zhou et al , ). The total run time of the method per sample was 2.5 min, which was shorter than reported values (Huang et al , ; Padua et al , ; Qin et al , ; Tashtoush et al , ; Tsakalof et al , ; Zhou et al , ).…”

“…The maximum plasma concentration ( C max ) was 87.0 ± 34.3 ng/mL, the time of maximum plasma concentration ( T max ) was 6.3 ± 0.91 h, the area under the plasma concentration–time curve from 0 h to the time of last measurable concentration (AUC 0– t ) was 864 ± 359 ng h/mL, area under the plasma concentration–time curve from 0 h to infinity (AUC 0–∞ ) was 919 ± 379 ng h/mL, the half‐life of drug elimination at the terminal phase ( t 1/2 ) was 9.7 ± 2.2 h. These parameters were in accordance with those reported in the literatures (Tamimi et al , ; Zhou et al , ).…”

“…During recent years, liquid chromatography–mass spectrometry, LC‐MS/MS (Huang et al , ; Padua et al , ; Qin et al , ) and LC‐MS (Tashtoush et al , ; Tsakalof et al , ; Zhou et al , ) have been used in the determination of lisinopril. However, these methods need long analysis times (>3.5 min) or complicated and time‐consuming sample pretreatment procedures, which do not meet the requirement for high throughput and speed in biosample analysis.…”