目的:建立Beagle犬血浆中酒石酸美托洛尔对映体浓度的高效液相色谱荧光测定方法。方法:Beagle犬口服消旋体酒石酸美托洛尔100rag后取1.5h血样进样测定,手性色谱柱为Chiralcel OD—H,流动相为正己烷-异丙醇-二乙胺(65:35:0.1),荧光检测波长Ex和Em分别为267nm、290nm,柱温为25℃,流速为0.6ml/min,内标物为(S)-阿替洛尔。结果:酒石酸美托洛尔2种对映体检测浓度在10~2000ng/m1范围内线性关系良好,平均回收率为96.12%~116.9%(RSD〈7.6%)。结论:该分析方法选择性好、准确性高、重现性好,适于酒石酸美托洛尔对映体的药动学研究。
OBJECTIVE: To establish HPLC method for the determination of plasma metoprolol tartrate enantiomers in Beagle dogs. METHODS: Plasma samples were taken from Beagle dogs at 1.5h after oral administration of metoprolol tartrate 100mg, Chiralcel OD H was taken as the chiral chromatographic column,the mobile phase consisted of N - hexane - dimethyl carbinol - diethylamine (65 : 35 : 0.1) with a flow rate at 0.6ml/min ,the fluorescence detection wavelength Ex was 267nm and Em was 290nm, the column temperature was 25℃ and the internal standard was (S) atenolol. RESULTS: Good linear relationship was achieved when the detection concentration of metoprolol enantiomers was within the range of 10--2 000ng/ml, the average recovery was 96.12% -- 116.9% (RSD〈 7.6% ) .CONCLUSIONS:The method is selective,accurate and reproducible, and suitable for the pharmacokinetics study of metoprolol tartrate enantiomers. KEY WORDS Metoprolol tartrate; Enantiomers; HPLC; Fluorometric method; Beagle dog