Automated microbore LC with peak compression for the assay of GR138950 and its active metabolite in human serum

Abstract

Microbore LC with peak compression sample injection can facilitate improved methods in LC. The advantages of this approach were clearly illustrated in the automated, microbore LC-peak compression assay of GR138950, a novel non-peptide angiotensin II antagonist selective for the AT1 receptor and its active metabolite in human serum. An existing analytical method had insufficient sensitivity to fully monitor the pharmacokinetic profile of GR138950 and its active metabolite (GR205838) when low doses were administrated. Consequently a robust assay with a lower limit of quantification was required. This was achieved by developing an alternative and fully automated solid phase extraction procedure with on-line peak compression sample injection onto a microbore (2.1 mm i.d.) column by means of a Zymate robot. This method produced cleaner extracts, improved precision, and lower limit of quantitation (1 ng mL−1) than had been achieved with the previous method which had used conventional LC.