dc.contributor.author | Wong, Allan K. | |
dc.contributor.author | Ross, Benjamin P. | |
dc.contributor.author | Chan, Yiu-Ngok | |
dc.contributor.author | Artursson, Per | |
dc.contributor.author | Lazorova, Lucia | |
dc.contributor.author | Jones, Alun | |
dc.contributor.author | Toth, Istvan | |
dc.date.accessioned | 2006-07-22 | |
dc.date.accessioned | 2017-03-02T00:29:45Z | |
dc.date.available | 2015-05-25T05:41:52Z | |
dc.date.available | 2017-03-02T00:29:45Z | |
dc.date.issued | 2002 | |
dc.identifier.issn | 0928-0987 | |
dc.identifier.doi | 10.1016/S0928-0987(02)00078-7 | |
dc.identifier.uri | http://hdl.handle.net/10072/67386 | |
dc.description.abstract | PURPOSE: To synthesize a number of analogues of Leu-enkephalin with different lipophilicities and to develop an LC-MS method for determining the Caco-2 cell permeability values of these compounds. METHODS: A number of sugar and sugar plus lipoamino acid analogues of Leu-enkephalin were synthesized by solid-phase and solution methods. An LC-MS method was developed for analyzing the Caco-2 cell assay samples and validated against the traditional method using radiolabelled compounds. RESULTS: A sensitive and specific LC-MS assay was developed. Standard curves were linear in the range of 0.025-5 microM. Apparent permeability values determined by LC-MS and liquid scintillation counter were identical, for both a hydrophilic drug, cephalexin and a lipophilic Leu-enkaphalin analogue. Caco-2 permeability values for the analogues of Leu-enkephalin were determined and it was found that attachment of sugar or sugar and lipoamino acid to the Leu-enkephalin peptide resulted in an increase in the apparent permeability values compared to the native peptide, which was not transported across the Caco-2 cell monolayers. CONCLUSIONS: A rapid, generic LC-MS method for analyzing a range of compounds was developed. Attachment of a sugar or sugar and lipoamino acid to Leu-enkephalin improves the apparent permeability across Caco-2 cell monolayers. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier Science | |
dc.publisher.place | Amsterdam | |
dc.relation.ispartofpagefrom | 113 | |
dc.relation.ispartofpageto | 118 | |
dc.relation.ispartofissue | 3 | |
dc.relation.ispartofjournal | European Journal of Pharmaceutical Sciences | |
dc.relation.ispartofvolume | 16 | |
dc.subject.fieldofresearch | Pharmacology and Pharmaceutical Sciences | |
dc.subject.fieldofresearchcode | 1115 | |
dc.title | Determination of transport in the Caco-2 cell assay of compounds varying in lipophilicity using LC-MS: enhanced transport of Leu-enkephalin analogues. | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | c1x | |
gro.faculty | Griffith Health Faculty | |
gro.date.issued | 2015-05-25T05:41:52Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Chan, Yiu-Ngok | |