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Nema T.,National University of Singapore | Nema T.,Waters Pacific Pte. Ltd. | Chan E.C.Y.,National University of Singapore | Ho P.C.,National University of Singapore
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

Recent advances in monolithic columns have made them an alternative to traditional packed columns used in liquid chromatography as well as capillary electrochromatography (CEC). The monolithic columns have been extensively studied and shown to possess several advantages that make them a promising and potential substitute for the particle packed columns. A large number of papers relating to monolithic columns have been published every year, focusing on different preparation techniques, characteristic evaluations as well as applications. This review highlighted the latest development of monoliths for other modes of analytical chemistry. In particular, this review will highlight the application of monoliths for sample preparation which is an important step of the entire analysis. © 2013 Elsevier B.V.

Pasha M.K.,S BIO Pte Ltd | Jayaraman R.,S BIO Pte Ltd | Reddy V.P.,University of Groningen | Yeo P.,S BIO Pte Ltd | And 4 more authors.
Drug Metabolism Letters | Year: 2012

SB1317 (TG02) is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. To evaluate full potential of this development candidate, we conducted drug metabolism and pharmacokinetic studies of this novel anti-cancer agent. SB1317 was soluble, highly permeable in Caco-2 cells, and showed >99% binding to plasma from mice, dog and humans. It was metabolically stable in human and dog liver microsomes relative to mouse and rat. SB1317 was mainly metabolized by CYP3A4 and CY1A2 in vitro. SB1317 did not inhibit any of the major human CYPs in vitro except CYP2D6 (IC50=1 μM). SB1317 did not significantly induce CYP1A and CYP3A4 in human hepatocytes in vitro. The metabolic profiles in liver microsomes from preclinical species were qualitatively similar to humans. In pharmacokinetic studies SB1317 showed moderate to high systemic clearance (relative to liver blood flow), high volume of distribution (>0.6 L/kg), oral bioavailability of 24%, ~ 4 and 37% in mice, rats and dogs, respectively; and extensive tissue distribution in mice. The favorable ADME of SB1317 supported its preclinical development as an oral drug candidate. © 2012 Bentham Science Publishers.

Ritchie M.A.,Institute for Animal Health | Ritchie M.A.,Waters Pacific Pte. Ltd. | Hunt L.G.,Institute for Animal Health | Gill A.C.,Institute for Animal Health | Gill A.C.,Easter Bush Veterinary Center
International Journal of Mass Spectrometry | Year: 2013

Conversion of PrPC, the prion protein, to a conformationally altered isoform, PrPSc, is the major pathogenic event in the transmissible spongiform encephalopathies, a family of neurodegenerative diseases including bovine spongiform encephalopathy, Creutzfeldt-Jakob disease and scrapie. Known post-translational modifications to the protein include disulfide bridge formation, addition of a membrane anchor and N-linked glycosylation. We have previously identified the pro-collagen-like hydroxylation of proline 44 in a murine, recombinant prion protein expressed in Chinese hamster ovary cells and herein report the identification of a second pro-collagen-like modification in this protein. In a proportion of the molecules, Lys193, within the C-terminal, folded domain of the protein, is specifically modified to hydroxylysine with subsequent addition of two hexose units, assumed to be the collagen-like disaccharide modifier Gal-Glu. Proof of the existence of these modifications has been obtained by means of tandem mass spectrometry and Edman degradation. Molecular dynamics simulations show that these modifications lead to a pronounced stabilising effect on the β2-α2 loop, a region of PrP crucial for the disease-associated conversion. If present in vivo, these modifications may have important implications in PrP structure, interactions with ligands or may modulate PrP aggregation. © 2012 Elsevier B.V.

Gee P.T.,Palm Nutraceuticals Sdn Bhd | Liew C.Y.,Research Instruments Sdn Bhd | Thong M.C.,Matrix | Gay M.C.L.,Waters Pacific Pte. Ltd.
Food Chemistry | Year: 2016

We have developed a method for analysing vitamin E using ultra-performance convergence chromatography with a chromatographic runtime of 5.5 min. A well-resolved chromatogram with excellent precision in retention time revealed seven vitamin E components in the palm oil derived tocotrienol-rich fraction. The major vitamin E components were α-tocopherol, α-tocotrienol, γ-tocotrienol and δ-tocotrienol whereas the minor vitamin E components were α-tocomonoenol, β-tocotrienol and an unreported trace component. The new component was positively identified by high-resolution mass spectrometry as 2-methyl-2(4′,8′,12′-trimethyltrideca-7′,11′-dienyl)5,7,8-trimethylchroman-6-ol or α-tocodienol. © 2015 Elsevier Ltd. All rights reserved.

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