A simple HPLC-fluorescence method for the measurement of R,S-sotalol in the plasma of patients with life-threatening cardiac arrhythmias

Abstract

R,S-sotalol, a ß-blocker drug with class III antiarrhythmic properties, is prescribed to patients with ventricular, atrial and supraventricular arrhythmias. A simple and sensitive method based on HPLC-fluorescence is described for the quantification of R,S-sotalol racemate in 500 µl of plasma. R,S-sotalol and its internal standard (atenolol) were eluted after 5.9 and 8.5 min, respectively, from a 4-micron C 18 reversephase column using a mobile phase consisting of 80 mM KH 2 PO 4 , pH 4.6, and acetonitrile (95:5, v/v) at a flow rate of 0.5 ml/min with detection at l ex = 235 nm and l em = 310 nm, respectively. This method, validated on the basis of R,S-sotalol measurements in spiked blank plasma, presented 20 ng/ml sensitivity, 20-10,000 ng/ml linearity, and 2.9 and 4.8% intra-and interassay precision, respectively. Plasma sotalol concentrations were determined by applying this method to investigate five high-risk patients with atrial fibrillation admitted to the Emergency Service of the Medical School Hospital, who received sotalol, 160 mg po, as loading dose. Blood samples were collected from a peripheral vein at zero, 0. ng/ml, T MAX = 1.8 h, AUC T = 10645 ng h -1 ml -1 , K ab = 1.23 h -1 , a = 0.95 h -1 , ß = 0.09 h -1 , t(1/2)ß = 7.8 h, Cl T /F = 3.94 ml min -1 kg -1 , and Vd/F = 2.53 l/kg. A good systemic availability and a fast absorption were obtained. Drug distribution was reduced to the same extent in terms of total body clearance when patients and healthy volunteers were compared, and consequently elimination half-life remained unchanged. Thus, the method described in the present study is useful for therapeutic drug monitoring purposes, pharmacokinetic investigation and pharmacokinetic-pharmacodynamic sotalol studies in patients with tachyarrhythmias.

Development of a validated spectrofluorimetric method for assay of sotalol hydrochloride in tablets and human plasma: application for stability-indicating studies

“…Based on the previously reported HPLC-fluorescence method [15], the fluorescence intensity was examined at 310 nm after excitation at 235 nm. As a consequence, the present work aims at discovering a new technique for the analysis of SOT in tablets and human plasma in addition to studying the stability of SOT under various stress conditions, according to the ICH guidelines.…”

“…Different spectrophotometric methods were reported for the determination of SOT based on the formation of charge transfer complex with 4-chloro-7-nitrobenzofurazan (NBD-Cl) reagent [7], derivative spectrophotometry [8,9] and chemometric-assisted spectrophotometry [10]. The reported chromatographic methods for SOT determination include HPLC with UV detection [10][11][12][13], fluorescence detection [14][15][16][17][18][19][20] and MS detection [21][22][23][24]. Stability of SOT in oral suspension was studied during its storage at different temperatures using HPLC in order to investigate its shelf-life stability [25,26].…”

A simple and sensitive LC‐MS/MS method for the determination of sotalol in rat plasma

“…Several liquid chromatographic (LC) methods have been described for the determination of sotalol with UV detection (Delamoye et al, 2004;Chiap et al, 2001;Musch et al, 1989) as well as fluorescence detection (FLD) (Musch et al, 1989;Zarghi et al, 2006;Rbeida et al, 2003;da Cunha et al, 2001;Laer et al, 2001;Santos et al, 2000). However, the sensitivity was not sufficient.…”