alexa In vitro Metabolic Stability Study of New Cyclen Based Antimalarial Drug Leads Using RP-HPLC and LC-MS/MS
ISSN: 2329-6798

Modern Chemistry & Applications
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Research Article

In vitro Metabolic Stability Study of New Cyclen Based Antimalarial Drug Leads Using RP-HPLC and LC-MS/MS

Apoorva V Rudraraju1, Mohammad F Hossain1, Anjuli Shrestha1, Prince NA Amoyaw1, Babu L Tekwani2 and Faruk Khan MO1*
1College of Pharmacy, Southwestern Oklahoma State University, 100 Campus Drive, Weatherford, Ok 73096, USA
2National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
Corresponding Author : Faruk Khan MO
College of Pharmacy, Southwestern Oklahoma State University 100 Campus Drive, Weatherford, Ok 73096, USA
Tel: 580-774-3064
E-mail: [email protected]
Received March 16, 2013; Accepted July 14, 2014; Published July 17, 2014
Citation: Rudraraju AV, Hossain MF, Shrestha A, Amoyaw PNA, Tekwani BL, et al. (2014) In vitro Metabolic Stability Study of New Cyclen Based Antimalarial Drug Leads Using RP-HPLC and LC-MS/MS. Mod Chem appl 2:129. doi:10.4172/2329-6798.1000129
Copyright: © 2014 Rudraraju AV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Metabolic stability of the new antimalarial drug leads is determined using Human Liver Microsome (HLM) and specific cytochrome P450 enzyme (CYP2C8) taking the clinically used antimalarial drug chloroquine as a positive control. Experiment is done using standard methods. All the assays were conducted in 0.5 M phosphate buffer at pH 7.4. In general the metabolic reaction was initiated by adding 1 mM NADPH and 0.5 mg of enzyme. Incubations were done with time frequency of 0 hr, 1 hr, and 2 hrs at 37°C and the reactions were terminated by adding acetonitrile in the equal amounts of the assay mixture taken. The samples were centrifuged for 15 minutes at 10,000×g at 4°C and an aliquot of the supernatant was subjected to analysis using HPLC as well as LC-MS to confirm the masses of the drug and/or metabolite(s), if any. While chloroquine was found to be metabolized in a predictable manner by both HLM and CYP2C8, the drug leads were metabolically stable at similar experimental conditions. This study demonstrated that the new drug leads are worth conducting further preclinical evaluations.

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