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Automated determination of venlafaxine in human plasma by on‐line SPE‐LC‐MS/MS. Application to a bioequivalence study
Author(s) -
Suenaga Eunice Mayumi,
Ifa Demian R.,
Cruz Alessandro Carvalho,
Pereira Renata,
Abib Eduardo,
Tominga Mineko,
Nakaie Clovis Ryuichi
Publication year - 2009
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200800629
Subject(s) - bioequivalence , chromatography , analyte , chemistry , venlafaxine , confidence interval , pharmacokinetics , selected reaction monitoring , calibration curve , detection limit , tandem mass spectrometry , mass spectrometry , mathematics , pharmacology , medicine , statistics , antidepressant , hippocampus
A new automated SPE‐LC‐ESI‐MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction‐monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25–200 ng/mL ( r >0.997). The between‐run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between‐run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth‐Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off‐line liquid–liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6–103.4% for AUC 0–48 h and 102.2–112.6% for C max . Since both 90% CI for AUC 0–48 h and C max were included in the 80–125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption.