Method Development
and Validation of Lercanidipine in Human Plasma by using LC-MS/MS and Comparison
of Pkpd Parameters of Lercanidipine and its Enantiomer
Umamaheshwari D. and Jayaprakash J.
Res. J. Biotech.; Vol. 20(1); 149-166;
doi: https://doi.org/10.25303/201rjbt1490166; (2025)
Abstract
Improved and Reliable Liquid Chromatography/ Tandem Mass Spectrometry (LC–MS/MS)
method has been developed and validated for the determination of lercanidipine in
human plasma. Plasma samples with lercanidipine-d3 as an internal standard (IS)
were prepared by solid phase extraction on Lercanidipine in human plasma by using
LC-MS/MS with symmetry C18 (75 x 4.6 mm, 3.5 μ) column. The developed method was
extended to bio-equivalence studies in which pharmacokinetic parameters (PK) like
concentration time profiles, Cmax, AUC0-t, AUC0-α, Tmax, T1/2, Kel, for lercanidipine
were estimated. Statistical methods were used to analyze the log- transformed pharmacokinetic
parameters AUC0-t, AUC0-α and Cmax for bioequivalence of each of these parameters.
Statistical analysis was performed using WinNonlin software. The matrix effect was
evaluated using standard-line slope, post-column infusion and post-extraction spiking
techniques.
IS's mean extraction recovery was >94%. Five quality controls had an average accuracy
(% CV) of 5.8% between batches and among batches. The results obtained for recemic
and enantiomers lercanidipine were under the acceptance criteria. It shows both
studies of lercanidipine under similar conditions and there is no in vivo conversion
of enantiomers. When the concentrations of the R-enantiomer and S-lercanidipine
were comparable, the R-enantiomer's presence protected the ester of S-lercanidipine
from first-pass metabolism and the choice to produce the recemic version of the
drug.
