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

Citation
Sr. Santos et al., A simple HPLC-fluorescence method for the measurement of R,S-sotalol in the plasma of patients with life-threatening cardiac arrhythmias, BRAZ J MED, 33(2), 2000, pp. 199-204
Citations number
20
Categorie Soggetti
Medical Research General Topics
Journal title
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
ISSN journal
0100879X → ACNP
Volume
33
Issue
2
Year of publication
2000
Pages
199 - 204
Database
ISI
SICI code
0100-879X(200002)33:2<199:ASHMFT>2.0.ZU;2-3
Abstract
R,S-sotalol, a beta-blocker drug with class III antiarrhythmic properties, is prescribed to patients with ventricular, atrial and supraventricular arr hythmias. A simple and sensitive method based on HPLC-fluorescence is descr ibed for the quantification of R,S-sotalol racemate in 500 mu l 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 reverse-phase column using a mo bile 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 lambda(ex) = 235 nm and lam bda(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 precisi on, respectively. Plasma sotalol concentrations were determined by applying this method to investigate five high-risk patients with atrial fibrillatio n admitted to the Emergency Service of the Medical School Hospital, who rec eived sotalol, 160 mg po, as loading dose. Blood samples were collected fro m a peripheral vein at zero, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 a nd 24.0 h after drug administration. A two-compartment open model was appli ed. 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), alpha = 0.95 h(-1), beta = 0.09 h(-1), t(1/2)beta = 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 tota l body clearance when patients and healthy volunteers were compared, and co nsequently elimination half-life remained unchanged. Thus, the method descr ibed in the present study is useful for therapeutic drug monitoring purpose s, pharmacokinetic investigation and pharmacokinetic-pharmacodynamic sotalo l studies in patients with tachyarrhythmias.