da Cunha L C, Gondim F A, de Paola A A, Barros I C, Santos S R
Faculdade de Farmácia da UFG, Escola Paulista de Medicina-UNIFESP, Brazil.
Boll Chim Farm. 2001 Nov-Dec;140(6):448-54.
A simplified high performance chromatographic method (HPLC) was performed for sotalol enantiomers in plasma samples for purposes of investigation of the kinetic disposition of racemic sotalol in cardiac arrhythmic patients under multiple dose and multidrug therapy regimens. After addition of NaCl:Na2CO3 (4:1) and plasma protein precipitation by acetonitrile:methanol mixture (1:1) the supernatant was evaporated. The residue containing sotalol racemate was submitted to derivatization reaction with (-)-menthylcloroformate to R(-)- and S(+)-sotalol diastereoisomers. The diastereoisomers were resolved in HPLC, by a C18 column with fluorescent detection under lexcitation = 235 nm and lemission = 310 nm. The retention times for R- and S-sotalol were 20 and 22 minutes while that of internal standard S(-)-atenolol, was 17 minutes. The detection limit for each enantiomer was 12.5 ng/mL and intra-day/inter-day coefficients of variation were less than 10% for each enantiomer within a concentration range of 200 and 2000 ng/mL. The method was appropriate for the objective proposed.
为了研究在多剂量和多药治疗方案下心律失常患者中消旋索他洛尔的动力学处置情况,采用一种简化的高效液相色谱法(HPLC)对血浆样本中的索他洛尔对映体进行分析。加入NaCl:Na₂CO₃(4:1)并用乙腈:甲醇混合物(1:1)进行血浆蛋白沉淀后,将上清液蒸发。将含有索他洛尔外消旋体的残渣与(-)-氯甲酸薄荷酯进行衍生化反应,生成R(-)-和S(+)-索他洛尔非对映异构体。在HPLC中,通过C18柱在激发波长λex = 235 nm和发射波长λem = 310 nm下进行荧光检测来分离非对映异构体。R-和S-索他洛尔的保留时间分别为20分钟和22分钟,而内标S(-)-阿替洛尔的保留时间为17分钟。每个对映体的检测限为12.5 ng/mL,在200至2000 ng/mL的浓度范围内,每个对映体的日内/日间变异系数均小于10%。该方法适用于所提出的目标。