LC-MS/MS method for the determination of the prodrug aripiprazole lauroxil and its three metabolites in plasma and its application to in vitro biotransformation and animal pharmacokinetic studies

LC-MS/MS method for the determination of the prodrug aripiprazole lauroxil and its three... A sensitive and selective LC-MS/MS method for determination of the prodrug aripiprazole lauroxil (AL) and the three metabolites (N-hydroxymethyl aripiprazole [NHA], aripiprazole [ARP], and dehydro aripiprazole [DHA]) in plasma was developed using ARP-d8 as an internal standard. The analytes were determined on an AB Sciex Triple Quad™ 4500 system using positive ion electrospray ionization and selected multiple reaction monitoring mode. Solid phase extraction was applied for sample preparation for AL, ARP, and DHA, and protein precipitation for NHA. Chromatographic separation was performed on an Agilent Eclipse XDB-CN column (100 × 2.1 mm i.d., 3.5 μm) using the mobile phase of water and acetonitrile (25:75, v/v) containing 0.1% formic acid with a flow rate of 0.5 mL/min. The linear ranges for AL, NHA, ARP, and DHA were 0.5–50 ng/mL, 1.0–50 ng/mL, 0.5–50 ng/mL, and 0.05–5.0 ng/mL, respectively. The average recovery in the plasma sample was stable and reproducible. The precision and accuracy of the intra- and inter-run were within assay variability criteria limits. The developed method was suitable for in vitro biotransformation studies in plasma and animal pharmacokinetic studies after intramuscular injection of AL formulations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Chromatography B Elsevier

LC-MS/MS method for the determination of the prodrug aripiprazole lauroxil and its three metabolites in plasma and its application to in vitro biotransformation and animal pharmacokinetic studies

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
1570-0232
eISSN
1873-376X
D.O.I.
10.1016/j.jchromb.2018.02.011
Publisher site
See Article on Publisher Site

Abstract

A sensitive and selective LC-MS/MS method for determination of the prodrug aripiprazole lauroxil (AL) and the three metabolites (N-hydroxymethyl aripiprazole [NHA], aripiprazole [ARP], and dehydro aripiprazole [DHA]) in plasma was developed using ARP-d8 as an internal standard. The analytes were determined on an AB Sciex Triple Quad™ 4500 system using positive ion electrospray ionization and selected multiple reaction monitoring mode. Solid phase extraction was applied for sample preparation for AL, ARP, and DHA, and protein precipitation for NHA. Chromatographic separation was performed on an Agilent Eclipse XDB-CN column (100 × 2.1 mm i.d., 3.5 μm) using the mobile phase of water and acetonitrile (25:75, v/v) containing 0.1% formic acid with a flow rate of 0.5 mL/min. The linear ranges for AL, NHA, ARP, and DHA were 0.5–50 ng/mL, 1.0–50 ng/mL, 0.5–50 ng/mL, and 0.05–5.0 ng/mL, respectively. The average recovery in the plasma sample was stable and reproducible. The precision and accuracy of the intra- and inter-run were within assay variability criteria limits. The developed method was suitable for in vitro biotransformation studies in plasma and animal pharmacokinetic studies after intramuscular injection of AL formulations.

Journal

Journal of Chromatography BElsevier

Published: Apr 1, 2018

References

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