Development and Validation of Liquid Chromatography Combined with Tandem Mass Spectrometry Methods for the Quantitation of Simalikalactone E in Extracts of Quassia amara L. and in Mouse Blood

• Published in: Phytochemical analysis 2015-03, Vol.26 (2), p.111-118
• Main Authors: Le, Hong Luyen, Jullian, Valérie, Claparols, Catherine, Vansteelandt, Marieke, Haddad, Mohamed, Cabou, Cendrine, Deharo, Eric, Fabre, Nicolas
• Format: Article
• Language: English
• Subjects: Animals; antimalarials; biological fluids; blood; Chromatography, High Pressure Liquid - methods; guidelines; intravenous injection; LC-MS; leaves; Life Sciences; Male; methanol; Mice; monitoring; pharmacokinetics; plant extract; plant extracts; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Leaves - chemistry; Plants, Medicinal; quantitation; Quassia - chemistry; Quassia amara; quassinoids; Quassins - blood; Quassins - chemistry; Quassins - isolation & purification; simalikalactone E; Simarouba amara; tandem mass spectrometry; Tandem Mass Spectrometry - methods; ultra-performance liquid chromatography
• ISSN: 0958-0344; 1099-1565
• DOI: 10.1002/pca.2542

INTRODUCTION: Simalikalactone E (SkE) from Quassia amara, has been proved to be a valuable anti‐malarial and anti‐cancer compound. As SkE is very scarce, methods of quantitation are needed in order to optimise its isolation process and to determine pharmacokinetic data. OBJECTIVE: To validate methods using liquid chromatography coupled to mass spectrometry for the quantitation of SkE in plant extracts and in biological fluids. METHODS: High‐ and ultrahigh‐performance liquid chromatography (UHPLC) coupled to ion trap mass spectrometry (MS) with single ion monitoring detection and to triple quadrupole‐linear ion trap tandem mass spectrometry with multiple reaction monitoring detection methods were developed. Validation procedure was realised according to the International Conference on Harmonisation guideline. Methanol extracts of dried Quassia amara leaves, and mouse‐blood samples obtained after various routes of administration, were analysed for SkE. RESULTS: Methods were validated and gave similar results regarding the content of SkE expressed per kilogram of dry leaves in the traditional decoction (160 ± 12 mg/kg) and in the methanol extract (93 ± 2 mg/kg). The recovery of the analyte from mouse blood ranged from 80.7 to 119.8%. Simalikalactone E was only detected using UHPLC–MS/MS (0.2 ± 0.03 mg/L) in mouse blood after intravenous injection: none was detected following intraperitoneal or oral gavage administration of SkE. CONCLUSION: The LC–MS methods were used for the quantitation of SkE in plant extracts and in mouse blood. These methods open the way for further protocol optimisation of SkE extraction and the determination of its pharmacokinetic data. Copyright © 2014 John Wiley & Sons, Ltd.