胺碘酮和心律平的高效液相色谱法分离与测定及其单用与合用时的药代动力学研究

A HPLC METHOD FOR SEPARATION AND QUANTITATION OF AMIODARONE AND PROPAFENONE IN PLASMA AND THEIR PHARMACOKINETIC STUDY

本文建立了用反相高效液相色谱法同时或分别测定胺碘酮和心律平血浓度的方法。本品的最低检测浓度分别为0.20mg/l和0.05mg/l,线性范围分别为0.20—5.00mg/I和0.05—5.00mg/I,一日内回收率分别为95.42%和98.55%,五日内回收率分别为95.91%和100.20%,平均回收率分别为95.66%和99.23%。对单用胺碘酮和心律平及二者合并用药后药代动力学的对比研究,发现6名健康志愿者在合并用药中,胺碘酮和心律平的Cl都较单用时低(p<0.01)。合用后心律平的K(p<0.05)及Vd(p<0.01)也降低,它的t1/2K及tmax都延长(p<0.05)。

Amiodarone and propafenone are often administered in combination for the treat-ment of refractory cardiac arrhythmia. It is necessary to study their plasma concentrations and phar-macokinetic behaviors for TDM. So a reversed-phase HPLC method using partisil ODS-2 (5um) co-lumn (250mmx?4.6mm) equiped with Tracor 951 and Shimadzu SPD)-MIA VIS-UV detector is de-veloped for the separation of amiodarone, propafenone, and the internal standard tardan. This methodhas the advantage of determining amiodarone and propafenone in the same plasma sample. The plasmasample is extracted 3 times with 4, 4, 3 ml ethyl ether. 20μl of the concentrated extract is taken to in-fect and chromatographed by the mobile phase CH_3OH: H_2O: CH_3COOH-CH_3COONa buffer:(C_2H_5)_3N(1000: 40: 10: 0.35v/v), with the flow rate of 1.5 ml/min. The retention time (t_R)of propafenone, tardan and amiodarone are 5.15, 6.66 and 10.03 min respectively. The linear rela-tionship of peak ratio to drug concentration are 0.20-5.00mg/l for amiodarone, and 0.05-5.00mg/lfor propafenone in plasma. The CV% of the method for both drugs is less than 4.5% either measusedwithin-day or between-days. Comparison of the pharmacokinetic behaviors between separate and combined administration ofamiodarone and propafenone with the above method is carried out in 6 normal volunteers. In the caseof combined administration to the 6 volunteers, the CL of both amiodarone and propafenone is lessthan those during separate administration (both p<0.01). The K and Vd of propafenone are de-creased (p<0.05, p<0.01 respectively), and its t1/2K and tmax are increased (P<0.05). Thera-peutic drug monitorring is therefore suggested to be mandatory when the two drugs are administered si-multaneously.