Simultaneous Determination of Venlafaxine and Its Main Active Metabolite O-Desmethyl Venlafaxine in Rat Plasma by LC-MS/MS

Abstract

A simple, sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of venlafaxine (VX) and its major active metabolite O-desmethyl venlafaxine (ODV) in rat plasma using carbamazepine as an internal standard (IS). The analytes from the biological matrix were extracted by liquid-liquid extraction using tert-butyl methyl ether (TBME). The HPLC separation of the analytes was performed on a water symmetry C18 (150 × 4.6 mm i.d., 5 µm) column, using a 10 mM ammonium formate:methanol (20:80 v/v) as mobile phase. The calibration curve concentration range was 10.10 to 8000.00 ng/mL for VX and ODV with coefficient of determination above 0.9970. The lower limit of quantification (LLOQ) of VX and ODV were 3.35 and 3.86 ng/mL, respectively. The intra-and inter-day coefficients of variation were within 15%.

Modern chromatographic and electrophoretic measurements of antidepressants and their metabolites in biofluids

“…An application of triple‐quadrupole mass spectrometry with enhanced resolution and mass capabilities by SIM mode (Jemal et al ., 2003), mass defect filtering (MDF) of liquid chromatography/high resolution mass spectrometry data (Zhu et al ., 2006) and a linear ion/orbitrap mass spectrometer (Peterman et al ., 2006) in metabolite characterization studies for NEF was also reported. LC‐MS/MS techniques were frequently applied for the assay of VEN and its metabolites along or simultaneously with other antidepressants in human serum (Kirchherr and Kühn‐Velten, 2006), blood (Castaing et al ., 2007; Kingbäck et al ., 2010), plasma (Bhatt et al ., 2005; Liu et al ., 2007a; Liu et al ., 2007b; Patel et al ., 2008b; Rajasekhar et al ., 2009; de Castro et al ., 2008; Kingbäck et al ., 2010; Qin et al ., 2010) and rat plasma (Shah et al ., 2009), as well as in raw sewage and wastewater (Lajeunesse et al ., 2008) samples. Among them, a stereoselective methods for plasma/blood determination of VEN and its metabolites using a Chirobiotic V column with a total run time of 35 and 13 min, was described by Kingbäck et al .…”

“…In this method, the recoveries were above 89.7 and 80.2% for the parent substance and its metabolite, respectively. An LC‐MS/MS assay of VEN and ODV in rat (Shah et al ., 2009) and human plasma (Rajasekhar et al ., 2009) was performed after LLE with tert ‐butyl methyl ether (TBME). This solvent, in alkaline (pH 8.5), was used by Liu et al .…”

Simple and Inexpensive Methods Development for Determination of Venlafaxine Hydrochloride from Its Solid Dosage Forms by Visible Spectrophotometry

“…Various methods have been reported for the estimation of venlafaxine hydrochloride in biological matrices such as plasma, which include the use of liquid chromatography (LC) with UV detection 4 , LC with electro spray ionization mass spectrometry 5 , LC with coulometric detection 6 , LC with fluorimetric detection 7,8 , LC with diode array detection 9,10 , gas chromatography-mass spectrometry (GC-MS) 11 , LC-MS 12 , LC-MS-MS 13,14 , and for the estimation in serum by using LC 15 , HPLC methods [16][17][18][19][20][21][22] , HPLC-MS/ESI 23 , voltammetry 24 ,Capillary Electrophoresis 25,26 , Flow injection analysis 27 . Stability indicating methods have also been reported for its in vitro determination in gastric and intestinal fluids 28 and pharmaceutical formulations 29 , few UV [30][31][32][33] and Visible Spectrophotometry [34][35][36][37][38] .…”

Solid Phase Extraction and Lc-MS/MS Method for Quantification of Venlafaxine and Its Active Metabolite O-Desmethyl Venlafaxine in Rat Plasma

“…Several researchers have worked on the analytical development of the target drug using different techniques including capillary electrophoresis [9][10][11][12], capillary chromatography [13], and LC-MS/MS [14][15][16][17][18][19][20]. Although, few reported methods are available for quantitative analysis of VEN and ODV.…”