A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using solid phase extraction for the simultaneous determination of plasma concentrations of enalapril and enalaprilate in hypertensive patients treated with different pharmaceutical formulations.
Enalapril maleate, available on the market in a variety of different pharmaceutical formulations, is commonly used for the control of systemic arterial hypertension. Many therapeutical failures have been reported thus far in clinical practice with respect to switching between different pharmaceutical formulations of the same product during pharmacological therapy. In the present study, plasma concentrations of enalapril and enalaprilate were measured in hypertensive patients undergoing treatment with different pharmaceutical formulations.


METHODS
Pharmaceutical formulations studied included the reference brand product, a generic formulation, and a third drug product marketed as "similar"; plasma samples were obtained from 30 hypertensive volunteer patients. Drug was extracted from the plasma by solid phase extraction and determined by liquid chromatography-tandem mass spectrometry. The method was validated for the main analytical parameters.


RESULTS
The analytical method developed in this study, using liquid chromatography-tandem mass spectrometry, was confirmed as suitable for application in the determination of plasma concentrations in patients and subsequently revealed statistically significant differences in plasma concentrations between the 3 treatment groups.


CONCLUSIONS
Such differences reinforce the hypothesis that the bioequivalence tests currently proposed by the regulatory authorities to promote interchangeability between pharmaceutical formulations may not in fact represent a definitive parameter for guaranteeing similar plasma concentrations.
Lima
Dione M
DM
Laboratory of Pharmaceutical Technology and Drug Delivery Systems, School of Pharmacy, Federal University of Goiás, Praça Universitária c/1a, Avenida, Goiânia, Goiás, Brazil.
Mundim
Iram M
IM
Jardim
Paulo César B V
PC
Jardim
Thiago S V
TS
Diniz
Danielle G A
DG
Lima
Eliana M
EM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004656:Enalapril / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D015773:Enalaprilat / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D057230:Limit of Detection; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D015773:Enalaprilat