High-performance liquid chromatographic assay of indomethacin and its application in pharmacokinetics in healthy volunteers.

A new sensitive high-performance liquid chromatographic method for indomethacin from plasma on a reversed-phase column (C18) has been developed. The method involves precipitation of plasma with perchloric acid followed by diethyl ether extraction. The assay is quantitative down to 0.25 microgram ml-1 from a 200-microliters aliquot of plasma with a detection limit of 0.1 microgram ml-1 and a recovery of approximately 90%. The method was applied to single-dose studies with volunteers under various dietary restrictions. The results of these studies indicated that intrasubject variability within these regimens may be as important a factor as the intersubject variability already documented for this drug. These results have important implications in the determination of bioavailability and pharmacokinetic parameters of this drug.