Ent/13/1/Page 13 ofspectrometer; LLE: Liquid-liquid extraction; LLOQ: Reduced limit of quantification; MMV: Medicines for Malaria

Ent/13/1/Page 13 ofspectrometer; LLE: Liquid-liquid extraction; LLOQ: Reduced limit of quantification; MMV: Medicines for Malaria Venture; MRM: Multiple reaction β adrenergic receptor Antagonist web monitoring; MTT: (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide; Nom: Nominal; OIS: On-instrument stability; PK: Pharmacokinetic; QC: Good quality handle; S/N: Signal-to-Noise ratio; SPVS: Method overall performance verification sample; ULOQ: Upper limit of quantification. Competing interests The authors declare that they’ve no competing interests. Authors’ contributions ETA Created and validated the LC-MS/MS assay for the quantitative determination of TK900D and TK900E in mouse blood, and applied the assay for PK-evaluation in the analytes; performed the data acquisition and interpretation from the results presented in the manuscript; compiled data and presented it in the form because it appears in the manuscript. MT synthesized the compounds and supplied us with in vitro activity data. LG assisted with the evaluation from the PK-properties using PK-summit computer software. LW, KJS and JHW edited, revised and accepted the manuscript, which is a part of ETA’s PhD project. KC revised the manuscript. The final version with the manuscript has been read and accepted by all the authors. Acknowledgments We would prefer to acknowledge the following institutions for their contribution towards the completion of this study: PAREXEL International clinical research organization, Bloemfontein, South Africa, where the analytical perform was carried out; the PK laboratory and also the animal unit of the pharmacology department in the University of Cape Town, exactly where the animal work was completed; the University of your Cost-free State plus the Technology and Human PRMT1 Inhibitor drug Sources for Business Programme (THRIP) for financial support; the University of Cape Town, the South African Healthcare Study Council plus the South African Analysis Chairs initiative with the Division of Science and Technologies, administered through the South African National Study Foundation are gratefully acknowledged for assistance (KC); the South African Health-related Investigation Council for financial assistance (self-initiated research grant ?Lubbe Wiesner). Author information 1 Division of Clinical Pharmacology, Division of Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa. 2PAREXEL?International Clinical Analysis Organisation, Private Bag X09, Brandhof 9300, Bloemfontein, South Africa. 3Department of Chemistry, University with the Free State, PO Box 339, Bloemfontein 9300, South Africa. 4Department of Chemistry, University of Cape Town, Rondebosch 7701, Cape Town, South Africa. 5Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch 7701, Cape Town, South Africa. Received: 19 November 2013 Accepted: 28 January 2014 Published: 31 January 2014 References 1. World Wellness Organization Media Centre: Malaria Reality Sheet No. 94. April 2012, Retrieved: December 18, 2012; from: who.int/ mediacentre/factsheets/fs094/en/, pp. 1. two. Millennium Project: International Burden of Malaria. Retrieved: December 25, 2011; from: unmillenniumproject.org/documents/GlobalBurdenofMalaria.pdf. three. Bawa S, Kumar S, Drabu S, Kumar R: Structural modifications of quinolonebased antimalarial agents: Recent developments. J Pharm Bioallied Sci 2010, 2:64?1. 4. Ridley RG, Hofheinz W, Matile H, Jaquet C, Dorn A, Masciadri R, Jolidon S, Richter WF, Guenzi A, Girometta M, Urwyler H, Huber W, Thaithong S, Peters W: 4-aminoquinoline analogues of chloroquine with shortened si.