TY - JOUR
T1 - Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry
T2 - Application to the analysis of drug-drug interaction
AU - Liu, Yijin
AU - Jann, Michael
AU - Vandenberg, Chad
AU - Eap, Chin B.
AU - Shamsi, Shahab A.
N1 - Funding Information:
This work was supported by NIH (Grant # R01-GM062314 ). Yijin Liu would like to thank Molecular Basis of Disease MBD program for the support on this work.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/11/13
Y1 - 2015/11/13
N2 - To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (. O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl. -L,. L-leucylalaninate (poly-. L,. L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15. min after optimizing the buffer pH, poly-. L,. L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150-5000. ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30. ng/mL and 21. ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy.
AB - To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (. O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl. -L,. L-leucylalaninate (poly-. L,. L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15. min after optimizing the buffer pH, poly-. L,. L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150-5000. ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30. ng/mL and 21. ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy.
KW - Enantioseparation
KW - MKEC-ESI-MS/MS
KW - Poly-L,L-SULA
KW - Venlafaxine/O-desmethylvenlafaxine
UR - http://www.scopus.com/inward/record.url?scp=84945473245&partnerID=8YFLogxK
U2 - 10.1016/j.chroma.2015.09.088
DO - 10.1016/j.chroma.2015.09.088
M3 - Article
C2 - 26460073
AN - SCOPUS:84945473245
SN - 0021-9673
VL - 1420
SP - 119
EP - 128
JO - Journal of Chromatography A
JF - Journal of Chromatography A
ER -