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 administrati on of UDCA-containing dosage forms. The plasma samples after solid-phase ex traction with silica-based C-18- and strong anion exchange cartridges were assayed by gas chromatography-mass spectrometry (GC-MS) using selected-ion monitoring. The hexafluoroisopropyl trifluoroacetate ester derivative of UD CA 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 sim ple high-performance liquid chromatographic (HPLC) method with on-line samp le purification. This analytical protocol was used to investigate the pharm acokinetic of a new sustained-release capsule of UDCA in comparison with a reference immediate-release preparation after single oral administration. S tatistical evaluation of the area under the plasma concentration-time curve s indicated that two Formulations are equivalent with regard to the amount of drug absorbed. However, pharmacokinetic data showed that with the sustai ned-release preparation a significantly delayed mean peak plasma level was reached compared with the reference preparation. Moreover, the immediate- a nd extended-release capsules were found to achieve a comparable degree of b iliary enrichment with UDCA.