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Simultaneous assessment of lipid classes and bile acids in human intestinal fluid by solid-phase extraction and HPLC methods
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2007 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 48, no 1, 242-251 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the study reported here was to develop a method for the determination of lipid classes in intestinal fluids, including bile acids (BAs). A solid-phase extraction (SPE) method using C18 and silica columns for the separation of BAs, phospholipids (PLs), and neutral lipids (NLs), including free fatty acids, has been developed and validated. Fed-state small intestinal fluid collected from humans was treated with orlistat to inhibit lipolysis and mixed with acetic acid and methanol before SPE to maximize lipid recoveries. BAs, PLs, and NLs were isolated using lipophilic and polar solvents to promote elution from the SPE columns. The different lipid classes were subsequently analyzed using three separately optimized HPLC methods with evaporative light-scattering detectors. High recoveries (>90%) of all lipids evaluated were observed, with low coefficients of variation (<5%). The HPLC methods developed were highly reproducible and allowed baseline separation of nearly all lipid classes investigated. In conclusion, these methods provide a means of lipid class analysis of NLs, PLs, and BAs in human fed-state small intestinal fluid, with potential use in other fluids from the intestinal tract and animals.

Place, publisher, year, edition, pages
2007. Vol. 48, no 1, 242-251 p.
Keyword [en]
solid-phase extraction, high-performance liquid chromatography, evaporative light scattering, neutral lipids, phospholipids
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-94994DOI: 10.1194/jlr.D600035-JLR200ISI: 000243130000026PubMedID: 17062898OAI: oai:DiVA.org:uu-94994DiVA: diva2:169038
Available from: 2006-10-19 Created: 2006-10-19 Last updated: 2011-02-18Bibliographically approved
In thesis
1. Drug Dissolution under Physiologically Relevant Conditions In Vitro and In Vivo
Open this publication in new window or tab >>Drug Dissolution under Physiologically Relevant Conditions In Vitro and In Vivo
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The general aim of the present project was to increase the understanding of the in vivo dissolution of poorly soluble drugs and thereby improve possibility to predict in vivo solubility from substance properties. Increased understanding of the in vivo limitations of drug solubility could potentially also generate ideas for improved formulation principles for poorly soluble compounds and more relevant in vitro dissolution test methods used in formulation development.

The dynamic gastrointestinal secretory and enzymatic responses to a liquid meal were studied in human intestinal fluid (HIF) by in vivo perfusion of a nutritional drink. The main diversity found compared to simulated intestinal fluids was the presence of dietary lipids in fed human intestinal fluid. This difference was showed to be of importance in the solubility of low soluble drugs, since this parameter was underestimated in the simulated fluid. Thus suggesting that simulated intestinal fluids should be prepared with the addition of dietary lipids for better in vitro in vivo predictions.

Solubility and dissolution determinations in fasted and fed HIF showed that the solubility was higher in fed state fluid, probably owing to the higher concentration of lipids in this media. The higher solubility was correlated to both the lipophilicity and aqueous solubility of the drug. The dissolution rate also increased, but not to the same extent as the solubility. These findings need to be considered in the design of in vitro models and in the prediction of food effects on oral bioavailability of poorly soluble drugs.

In addition, an in vivo porcine perfusion study was performed to investigate importance of different mechanisms in food-drug interactions. The results showed that solubilisation might be a more important factor than P-gp inhibition for food-related effects on the intestinal absorption kinetics of Class II drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 39
Biopharmacy, solubility, drug dissolution, food effects, poorly soluble drugs, P-gp inhibition, drug absorption, pemeability, bile acids, phospholipids, human intestinal fluid, simulated intestinal fluid, neutral lipids, solid phase extraction, HPLC, Efflux, Biofarmaci
urn:nbn:se:uu:diva-7195 (URN)91-554-6684-2 (ISBN)
Public defence
2006-11-10, B41, Uppsala Biomedicinska Centrum, Husargatan 3, Uppsala, 10:15
Available from: 2006-10-19 Created: 2006-10-19Bibliographically approved

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Abrahamsson, BertilLennernäs, Hans
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