Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Validation of a LC-MS/MS Method for Quantitative Analysis of MELK Inhibitor OTS167 in Mouse Serum: Application to a Pharmacokinetic Study

Wei Peng Yong
,
Vinod Vijay Subhash
,
Mitchell Qin-Ying Ee
,
Nicholas Syn
,
Mei Shi Yeo
,
Xiaoqiang Xiang
,
Andrea Li-Ann Wong
,
Alan Prem Kumar
ORCID logo ,
Gautam Sethi
,
Kam Man Hui
,
Paul Chi-Lui Ho
,
Boon Cher Goh
,
Lingzhi Wang
*
Version 1 : Received: 17 August 2018 / Approved: 17 August 2018 / Online: 17 August 2018 (15:15:12 CEST)

How to cite: Yong, W.P.; Subhash, V.V.; Ee, M.Q.; Syn, N.; Yeo, M.S.; Xiang, X.; Wong, A.L.; Kumar, A.P.; Sethi, G.; Hui, K.M.; Ho, P.C.; Goh, B.C.; Wang, L. Validation of a LC-MS/MS Method for Quantitative Analysis of MELK Inhibitor OTS167 in Mouse Serum: Application to a Pharmacokinetic Study. Preprints 2018, 2018080314. https://doi.org/10.20944/preprints201808.0314.v1 Yong, W.P.; Subhash, V.V.; Ee, M.Q.; Syn, N.; Yeo, M.S.; Xiang, X.; Wong, A.L.; Kumar, A.P.; Sethi, G.; Hui, K.M.; Ho, P.C.; Goh, B.C.; Wang, L. Validation of a LC-MS/MS Method for Quantitative Analysis of MELK Inhibitor OTS167 in Mouse Serum: Application to a Pharmacokinetic Study. Preprints 2018, 2018080314. https://doi.org/10.20944/preprints201808.0314.v1

Abstract

A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the evaluation of OTS167 pharmacokinetics in mouse serum. SN-38 was optimized to be selected as the internal standard. Chromatographic separation was performed on a BDS Hypersil C18 column (100 x 2.1 mm, 5 µm) using gradient elution with mobile phase solvent A as water containing 0.1% formic acid and solvent B as acetonitrile containing 0.1% formic acid. The analysis was carried out using multiple reaction monitoring (MRM) with a triple-quadrupole mass spectrometer operated in the positive electrospray ionization mode. Mass transitions of 487.2 > 348.0 and 393.2 > 349.2 were monitored for OTS167 and SN-38 respectively. The standard calibration curve demonstrated high linearity at a range of 5-1000 ng/mL, with a coefficient of determination (r2) ≥ 0.996. The accuracy for OTS167 ranged from 92.3% to 102.2% and the precision was ≤ 12.7%. Recovery was consistent at about 83% to 89%. No significant matrix effect was observed. This method was successfully applied to monitor the pharmacokinetic profiles in mice over 24 h after ingestion of 5 mg/kg of OTS167. Maximum serum concentrations (3197 ng/mL) of OTS167 was observed at 1.67 hour after OTS167 ingestion via garage at 5 mg/kg and area under the curve (AUC) was 28579 h*ng/mL, suggesting that OTS167 can be quickly absorbed after oral administration.

Keywords

MELK inhibitor; OTS167; LC-MS/MS; Pharmacokinetics, mouse serum

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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