ABSTRACT
Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R- and S-VFX. The two enantiomers of VFX exhibit different pharmacological activities: R-VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S-VFX inhibits only the serotonin one. R- and S-VFX are metabolized in the liver to the respective R- and S-O-desmethylvenlafaxine (ODVFX), R- and S-N-desmethylvenlafaxine (NDVFX), and R- and S-N,O-didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R- and S-VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.
Subject(s)
Desvenlafaxine Succinate , Venlafaxine Hydrochloride , Antidepressive Agents , Chromatography, Liquid , Cyclohexanols/analysis , Cyclohexanols/chemistry , Cyclohexanols/isolation & purification , Cyclohexanols/pharmacokinetics , Desvenlafaxine Succinate/analysis , Desvenlafaxine Succinate/chemistry , Desvenlafaxine Succinate/isolation & purification , Desvenlafaxine Succinate/pharmacokinetics , Electrophoresis, Capillary , Humans , Stereoisomerism , Tandem Mass Spectrometry , Venlafaxine Hydrochloride/analysis , Venlafaxine Hydrochloride/chemistry , Venlafaxine Hydrochloride/isolation & purification , Venlafaxine Hydrochloride/pharmacokineticsABSTRACT
Duloxetine (DLX) is a widely used antidepressant drug belonging to the class of selective serotonin and norepinephrine reuptake inhibitors (SNRIs); its efficacy has been demonstrated in the treatment of not only major depressive disorders but also diabetic neuropathic pain, generalized anxiety disorder, fibromyalgia or stress urinary incontinence. It is a chiral substance and is used in therapy in the form of the enantiopure S-DLX, which is twice as active as R-DLX. Several methods have been published for the achiral and chiral determination of DLX in pharmaceuticals, biological materials and environmental samples, the majority using liquid chromatography and capillary electrophoresis coupled with different detection techniques (UV detection, fluorescence, mass spectrometry). The aim of the current review is to provide a systematic survey of the analytical techniques used for the determination of DLX from different matrices.