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. 2013 Dec;3(6):466-471.
doi: 10.1016/j.jpha.2013.05.002. Epub 2013 Jun 3.

Rapid sensitive validated UPLC-MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study

Sunil Kumar Dubey  1 , R N Saha  1 , Hemanth Jangala  1 , S Pasha  2
Affiliations

Rapid sensitive validated UPLC-MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study

Sunil Kumar Dubey et al. J Pharm Anal. 2013 Dec.

Abstract

A new ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-MS/ESI) method for simultaneous determination of venlafaxine (VEN) and its metabolite O-desmethylvenlafaxine (ODV) in rat plasma has been developed and validated using Venlafaxine d6 as the internal standard. The compounds and internal standard were extracted from plasma by solid phase extraction. The UPLC separation of the analytes was performed on ACQUITY UPLC® BEH Shield RP18 (1.7 µm, 100 mm×2.1 mm) column, using isocratic elution with mobile phase constituted of water (containing 2 mM ammonium acetate): acetonitrile (20:80, v/v) at a flow rate of 0.3 mL/min. All of the analytes were eluted within 1.5 min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer, operating in multiple reaction monitoring (MRM) and positive ion mode. The precursor to product ion transitions monitored for VEN, ODV and Venlafaxine d6 were m/z 278.3→121.08, 264.2→107.1 and 284.4→121.0, respectively. The developed and validated method was used for the pharmacokinetic study of VEN in rats.

Keywords: Metabolite; O-desmethylvenlafaxine; UPLC–MS/ES; Venlafaxine.

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Figures

Fig. 1
Fig. 1
Chemical structure of each compound: Venlafaxine (VEN), O-desmethylvenlafaxine (ODV) and Venlafaxine d6.
Fig. 2
Fig. 2
Representative chromatograms of (A) VEN, (B) ODV and (C) Venlafaxine d6.
Fig. 3
Fig. 3
Plasma concentration–time profile of VEN and ODV after oral administration of 30 mg/kg of venlafaxine hydrochloride in rats.
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