Liquid chromatography tandem mass spectrometry assay for simultaneous determination of venlafaxine and its active metabolite in human plasma and its application to a bioequivalence study

Jun ZHANG

ABSTRACT

OBJECTIVE:

To establish a liquid chromatography tandem mass spectrometry (LC-MS-MS) method for simultaneous determination of venlafaxine (Ven) and its active metabolite, O-desmethylvenlafaxine (ODV), in human plasma, and to investigate the pharmacokinetics and bioequivalence of Ven and ODV in venlafaxine hydrochloride capsules in Chinese healthy volunteers.

METHODS:

Twenty-two volunteers took a single oral dose (50 mg) of venlafaxine hydrochloride capsules by 2-way crossover design. The concentrations of Ven and ODV in plasma were determined by HPLC-MS-MS. The pharmacokinetic parameters were calculated by BAPP software.

RESULTS:

Blood samples were deproteinized . The calibration curves of Ven and ODV were linear in the range from 1.99 to 510 μg · L-1 (r=0.9997) and 1.96 to 501 μg · L-1 (r=0.9999), respectively. The relative recovery was 92.2%-105.9%. The intra-day and inter-day RSDs were less than 10.5%. The pharmacokinetic parameters of test and reference capsules of Ven were as follows ρmax were (68.90 ± 23.8) and (69.81 ± 23.73) μg · L-1, tmax were (2.2 ± 0.7) and (1.9 ± 0.8) h, t1/2 were (5.0 ± 1.1) and (4.9 ± 1.6) h, AUC0-24 were (547.91 ± 288.66) and (592.70 ± 330.70) μg · h · L-1, respectively; the pharmacokinetic parameters of test and reference capsules of ODV were as follows; ρmax were (73.88 ± 21.18) and (73.96 ± 22.09) μg · L-1, tmax were (3.8 ± 1.8) and (4.0 ± 1.6) h, t1/2 were (8.7 ± 1.8) and (8.9 ± 1.9) h, AUC0-48 were (1 224.41 ± 239.46) and (1243.53 ± 287.19) μg · h · L-1, respectively. The relative bioavalabilities of Ven and ODV in the test capsules were (107.8 ± 22.0)% and (99.6 ± 10.7)%, respectively.

CONCLUSION:

The HPLC-MS-MS method for simultaneous determination of Ven and ODV in plasma is proved to be sensitive, accurate and convenient. The reference and test capsules are bioequivalent. Copyright 2012 by the Chinese Pharmaceutical Association.