Pharmacokinetic study of a new angiotensin-AT1 antagonist by HPLC.
Recently an innovative novel class angiotensin-AT1 antagonist has been developed by Rottapharm. In this study, we present a validated method for detecting CR 3834 in biological matrices using high-performance liquid chromatography (HPLC) with diode array detection. After oral administration (30mg/kg) to Wistar rats, the plasma and urine concentrations of CR 3834 and its potential metabolic products were determined. Moreover, the plasmatic time course in rats has been determined after intravenous (IV) administration of CR 3834 (5mg/kg). Biological samples (0.5ml of plasma and 1ml of urine) were purified using solid-phase extraction (SPE) of analytes and the internal standard Idebenone, 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1-4-benzoquinone. A chromatographic separation was performed on an Adsorboshere C18 at 25 degrees C, with a pre-column of the same matrix; the eluent was made up of acetonitrile/acidified water with CF3COOH (pH 2.01) in ratio of 75:25 (v/v); the flow rate was 1.0ml/min and a 100microl loop. The lower limit of detection (LOD) was taken as 25ng/ml in plasma and 50ng/ml in urine samples. The lower limit of quantification (LOQ) was taken as 0.1 and 0.2microg/ml in plasma and urine samples, respectively. The procedures were validated according to international standards with a good reproducibility and linear response (r=0.9916 in plasma; r=0.9997 in urine). The coefficients of variation inter assay ranged between 2.579 and 4.951% in plasma, and between 0.813 and 2.460% in urine. Mean recovery for CR 3834 was 79% in plasma and 97% in urine samples. The experiments performed demonstrated that the method presented was suitable for determining this new angiotensin-AT1 antagonist in rat plasma and urine.
Rizzo
M
M
Dipartimento di Scienze Farmacobiologiche, Università degli Studi Magna Graecia di Catanzaro, Viale Europa, Contrada Germaneto, 88100 Catanzaro, Italy. rizzomilena@unicz.it
Ventrice
D
D
Casale
F
F
Caselli
G F
GF
Makovec
F
F
D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
D047228:Angiotensin II Type 1 Receptor Blockers