Determination of quinidine by high-performance liquid chromatography.

Abstract

Quinidine in serum was measured at 330 nm, after protein precipitation, with an alkyl phenyl reversed-phase chromatographic column by peak-height determination (external standards.) Sensitivity was 0.3 mg/liter, with linear response to at least 10 mg/liter serum. Interassay precision, measured on 20 consecutive days, gave a CV of 8.2% at 2 mg/liter of serum and 5.1% at 5 mg/liter. Quinine and primaquine are not separable from quinidine under the assay conditions, and dihydroquinidine and chloridazepoxide are only partly resolved. No assay interference was encountered with a series of control serum samples obtained from patients with various diseases, who were being treated with various drugs other than quinidine, except in one serum sample with a high bilirubin concentration (300 mg/liter). If such an assay interference is present, an alkaline extraction of quinidine before analysis has to be used. Results by our assay and those by a single-extraction fluorescence method correlated poorly (r=0.87), and the fluorescence assay gave 50% +/- 7% (SEM) higher values than our method, due to chromatographic separation of a major fluorescent non-phenolic metabolite of quinidine, which can also be measured by our assay.