吡喃霉素在乳腺癌患者体内的药代动力学

Pharmacokinetics of Pirarubicin in Patients With Breast Cancer

目的 :建立HPLC分离和检测人血浆中吡喃霉素 (Pir)的分析方法 ,并研究Pir在乳腺癌患者体内的药代动力学。方法 :以正定霉素为内标 ,1ml血浆加0 1ml(0 4mol/L ,pH=9 0)的氯化铵缓冲液碱化后以氯仿 -甲醇 (2∶1 ,v/v)混合溶剂提取2次。在Phe nomenex(C18)柱上 ,以0 04mol/L磷酸二氢钾 (pH=3 0)∶乙腈=68∶32为流动相 ,荧光检测波长480nm/550nm(Ex/Em )。结果 :血浆中Pir的线性范围5～1000ng/ml(r=0 9997) ,方法回收率为95 3 % ,日内及日间变异性RSD均小于5 % ;Pir在人体的药代动力学特征为开放性二室模型 ,消除相半衰期T1/2β、清除率CLs、表观分布容积Vd及曲线下面积AUC分别依次为 (12 8±5 9)h、(128 3±52 6)L/(m2·h)、(1754 3±478 2)L/m2 和 (428 7±137 2)ng/(h·ml)。结论 :本方法适用于临床Pir的血药浓度监测和药代动力学研究。

AIM:To estabish a HPLC assay for the determination of pirarubicin(Pir) in plasma METHODS:Daunomycin(DM)was used as the internal standard Plasma samples were extracted with CHCl3∶CH3OH(2∶1) 0 4M NH4Cl buffer(pH=9 0)solution:CH2OH(1∶9)and the internal standard were added Separation was carried out on a 250mm×4 6mm(5μm)phenomenex column with 0 04M KH2PO4(pH=3 0)∶CH3CN(68∶32)as mobile phase Fluorescent detector was set at an excitation wavelength of 480nm and an emission wavelength of 550nm RESULTS:The calibration curves for serum Pir was linear over the range of 5～1 000ng/ml(r=0 9 997) The recovery of Pir was 95 3% The within-day and between-day variations were less than 5% T1/2β,CLs,Vd and AUC of Pir were(12 8±5 9)h,(128 3±52 6)L/(m2·h),(1 754 3±478 2)L/m2 and (428 7±137 2)ng/(h·ml),respectively CONCLUSION:The method is suited for monitoring blood concentration and pharmacokinetic study of Pir