Liquid chromatography assay for amlodipine: chemical stability and pharmacokinetics in rabbits.
Amlodipine is a long acting dihydropyridine calcium antagonist recently introduced for the treatment of angina and hypertension. In order to document its stability in vitro and to develop a pharmacokinetic model in rabbits, a new reversed-phase liquid chromatography (LC) assay with UV detection was developed. The method utilized a C18 column (250 x 4.6 mm i.d.) with a mobile phase composed of a mixture of methanol 0.04 M ammonium acetate-acetonitrile (38:38:24, v/v/v) containing 0.02% triethylamine (final pH 7.1). Under these conditions, the retention times of amlodipine and the internal standard desipramine were 10.6 and 12.9 min, respectively. Using 1 ml of plasma, sensitivity of the assay was 2.5 ng ml-1 at which the RSD was 11%. The standard curve was linear from 2.5 to 100 ng ml-1 (r2 = 0.990), and the mean RSD at this concentration range was 6.8%. The pharmacokinetic model was developed in rabbits which provides results similar to those in dogs, but at less expense. The assay was also applied to a stability study comparing amlodipine and nifedipine in pH 3 and pH 7 ammonium acetate buffers and in methanol. Amlodipine was considerably more stable than nifedipine under all conditions. Finally the assay was applied to a pharmacokinetic study in rabbits (n = 6) after a single 1 mg kg-1 intravenous dose. The mean half-life (t1/2) of amlodipine was 6.5 h, the systemic clearance (CL) was 4.8 l h-1 kg-1 and the apparent volume of distribution at steady state (Vdss) was 30.2 l kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Yeung
P K
PK
College of Pharmacy, Faculty of Health Professions, Dalhousie University, Halifax, Nova Scotia, Canada.
Mosher
S J
SJ
Pollak
P T
PT
D000085:Acetates / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008027:Light; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits
D000085:Acetates; D000097:Acetonitriles; D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine; C018824:ammonium acetate; C032159:acetonitrile