Microbore liquid chromatography with UV detection to study the in vivo passage of compound 21, a non-peptidergic AT2 receptor agonist, to the striatum in rats

A microbore liquid chromatography method coupled to UV detection was developed and validated in order to monitor the passage of compound 21 (C21), a non-peptide angiotensin II type 2 receptor agonist, to the striatum of rats. For this purpose, sampling from the striatum was performed using the in vivo microdialysis technique. Separations were performed on a C-18 microbore (1 mm id.) column using gradient elution. The retention time for C21 was found to be 6.3 min. The calibration curve was linear between 10 and 200 ng/ml with a correlation coefficient >= 0.999. The limit of detection and the limit of quantification were 3 and 10 ng/ml respectively. The intra-day and the inter-day precision (RSD%) ranged between 0.5 and 4.6% with an average recovery of 101.5 +/- 10.0% (mean +/- SD, n = 15). In vivo experiments were performed on rats to measure the concentration of C21 in striatal dialysates after intraperitoneal (10 or 50 mg/kg) or intravenous injection (10 mg/kg or 20 mg/kg) of C21 and suggest minimal passage of the compound to the striatum. (C) 2011 Elsevier B.V. All rights reserved.