Evaluation of ursodeoxycholic acid bioavailability from immediate- and sustained-release preparations using gas chromatography-mass spectrometry and high-performance liquid chromatography.
An improved procedure is presented for the determination of ursodeoxycholic acid (CAS 128-13-2, UDCA) in human plasma and bile after oral administration of UDCA-containing dosage forms. The plasma samples after solid-phase extraction with silica-based C18- and strong anion exchange cartridges were assayed by gas chromatography-mass spectrometry (GC-MS) using selected-ion monitoring. The hexafluoroisopropyl trifluoroacetate ester derivative of UDCA was selected for GC analysis since it is easily and rapidly prepared by a one-step reaction. Biliary UDCA levels were determined by a rapid and simple high-performance liquid chromatographic (HPLC) method with on-line sample purification. This analytical protocol was used to investigate the pharmacokinetic of a new sustained-release capsule of UDCA in comparison with a reference immediate-release preparation after single oral administration. Statistical evaluation of the area under the plasma concentration-time curves indicated that two formulations are equivalent with regard to the amount of drug absorbed. However, pharmacokinetic data showed that with the sustained-release preparation a significantly delayed mean peak plasma level was reached compared with the reference preparation. Moreover, the immediate- and extended-release capsules were found to achieve a comparable degree of biliary enrichment with UDCA.
Scalia
S
S
Dipartimentodi Scienze Farmaceutiche, Università di Ferrara, Italy.
Scagliarini
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R
Pazzi
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P
D000328:Adult; D019540:Area Under Curve; D001646:Bile / Q000737:chemistry; D001647:Bile Acids and Salts / Q000737:chemistry; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008863:Microspheres; D016037:Single-Blind Method; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D002214:Capsules; D003692:Delayed-Action Preparations; D014580:Ursodeoxycholic Acid