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

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Abstract

R,S-sotalol, a β-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 C18 reverse-phase column using a mobile phase consisting of 80 mM KH2PO4, pH 4.6, and acetonitrile (95:5, v/v) at a flow rate of 0.5 ml/min with detection at λ(ex) = 235 nm and λ(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, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0 h after drug administration. A two- compartment open model was applied. Data obtained, expressed as mean, were: C(MAX) = 1230 ng/ml, T(MAX) = 1.8 h, AUC(T) = 10645 ng h-1 ml-1, K(ab) = 1.23 h-1, α= 0.95 h-1, β = 0.09 h-1, t(1/2)β = 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.

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Santos, S. R., Papini, O., Omosako, C. E., Pereira, M. D., Quintavalle, T. B. C., Riccio, M. F., … Da-Luz, P. L. (2000). A simple HPLC-fluorescence method for the measurement of R,S-sotalol in the plasma of patients with life-threatening cardiac arrhythmias. Brazilian Journal of Medical and Biological Research, 33(2), 199–204. https://doi.org/10.1590/S0100-879X2000000200006

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