Determination of sotalol in human cardiac tissue by high-performance liquid chromatography.
A sensitive and quantitative reversed-phase HPLC method for the analysis of D,L-sotalol in human atria, ventricles, blood and plasma was developed. Sotalol was determined in about 100 mg of human right atria, left ventricles, and in 500 microliters of blood and plasma samples of patients undergoing coronary bypass surgery or heart transplantation. Patients were taking 80-160 mg of sotalol as an antiarrhythmic agent. Atenolol was used as an internal standard certifying high precision of measurement. Sotalol blood and plasma concentrations correlated linearly to the obtained signals from 26.5 ng/ml to 2.12 micrograms/ml. Sotalol tissue concentrations showed linearity between 0.27 ng/mg and 10.6 ng/mg wet weight. The limit of quantitation was 0.27 ng/mg at a signal-to-noise ratio of 10. Sotalol was extracted from homogenized tissue with a buffer solution (pH9) and the remaining pellet was extracted with methanol. The methanol extract was evaporated under nitrogen and reconstituted in buffer (pH3). The whole extract was cleaned by solid-phase column extraction, eluted with methanol, evaporated again, reconstituted in the mobile phase (acetonitrile-15 mM potassium phosphate buffer pH3, 17:83, v/v) and injected onto the HPLC column (Spherisorb C6 column, 5 microns, 150 x 4.6 mm I.D.). For the detection of sotalol, the UV wavelength was set to 230 nm. Recoveries of sotalol and atenolol in atria and ventricles were 65.6 and 75.0%, respectively. Intra- and inter-assay coefficients of variation for tissue concentrations were 3.38 and 6.14%, respectively. Intra- and inter-assay accuracy for determined tissue sotalol concentrations were 94.9 +/- 6.3 and 99.6 +/- 4.1%.
Läer
S
S
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Neumann
J
J
Scholz
H
H
Uebeler
P
P
Zimmermann
N
N
D000319:Adrenergic beta-Antagonists / Q000032:analysis*; D000889:Anti-Arrhythmia Agents / Q000032:analysis*; D001262:Atenolol / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D006325:Heart Atria / Q000737:chemistry; D006352:Heart Ventricles / Q000737:chemistry; D006801:Humans; D009206:Myocardium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013015:Sotalol / Q000032:analysis* / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001262:Atenolol; D013015:Sotalol