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Pharmaceutics 2018, 10(3), 123; https://doi.org/10.3390/pharmaceutics10030123

A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study

1
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
2
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
3
Department of Pharmacy, National University of Singapore, Singapore 117543, Singapore
4
Department of Haematology & Oncology, National University Cancer Institute, National University Health System, Singapore 119082, Singapore
5
Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China
6
Institute of Materials Research and Engineering (IMRE), ASTAR, Singapore 138634, Singapore
*
Authors to whom correspondence should be addressed.
Received: 2 July 2018 / Revised: 30 July 2018 / Accepted: 31 July 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Preclinical Pharmacokinetics and Bioanalysis)
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Abstract

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100 mm × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/mL range. The intra- and inter-day precisions for nimbolide were ≤12.6% and ≤13.9% respectively. Intra-day accuracy ranged from 96.9–109.3%, while inter-day accuracy ranged from 94.3–110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum, and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy. View Full-Text
Keywords: nimbolide; LC-MS/MS; mouse; serum; pharmacokinetics nimbolide; LC-MS/MS; mouse; serum; pharmacokinetics
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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. (CC BY 4.0).
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Wang, L.; Phan, D.-D.K.; Syn, N.; Xiang, X.; Song, H.; Thuya, W.L.; Yang, S.; Wong, A.L.-A.; Kumar, A.P.; Yong, W.P.; Sethi, G.; Ho, P.C.-L.; Goh, B.C. A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study. Pharmaceutics 2018, 10, 123.

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