剖宫产术中左旋布比卡因的血药浓度测定及胎盘转移初探

Placental transfer of levobupivacaine and its plasma concentration in cesarean section

目的:建立测定行剖宫产术的产妇及胎儿体内左旋布比卡因血药浓度的高效液相色谱法。通过检测胎儿娩出时母体血(MV)、脐静脉血(UV)的左旋布比卡因血药浓度,明确左旋布比卡因作为剖宫产术硬膜外麻醉药物时通过胎盘的情况。方法:色谱柱为 Zorbax extend C_(18)(5μm,4.6 mm×250 mm);流动相:磷酸盐缓冲液(磷酸氢二钠与磷酸二氢钠摩尔浓度1:1)-乙腈(35:65,pH=6.8),流速1.0 mL·min^(-1),柱温25℃,检测波长263 nm,进样量100 μL,样品处理采用蛋白沉淀法。选择30例正常剖宫产产妇,ASA Ⅰ-Ⅱ级,硬膜外给予0.5%左旋布比卡因25.2±1.1 mL,通过高效液相色谱法检测 MV、UV 中左旋布比卡因浓度.结果:本方法线性范围:0.025～1.0μg·mL^(-1),r=0.9998,最低检测浓度为0.01μg·mL^(-1);方法回收率96.1%～102.8%(n=5),日内 RSD 为1.3%～3.2%(n=5),日间 RSD 为3.1%～5.6%(n=5)。30例胎儿娩出时 Apgar 评分正常,母体血与脐静脉血的左旋布比卡因浓度分别为0.35±0.24μg·mL^(-1)、0.24±0.21μg·mL^(-1),平均 UV/MV 比值为0.72±0.34。胎儿娩出时 MV 中左旋布比卡因浓度始终高于 UV 中的浓度(P<0.01)。结论:0.5%左旋布比卡因很快通过胎盘,对胎儿没有明显影响,用于剖宫产硬膜外麻醉是安全有效的。

Objective：To establish an HPLC method for the determination levobupivacaine in maternal vein plasma and umbilical vein plasma. To assess transplacental passage of levobupivacaine by measuring the levels in maternal and umbilical plasma at the time of delivery when levobupivacaine was used as an agent in obstetric epidural anesthesia. Methods：Zorbax extend Cis column（5 μm,4.6 mm× 250 mm） was used;The mobile phase consisted of phosphate buffer （ sodium dihydrogan phospate： sodium phosphate dibasic anhydrous = 1：1 ） - acetonitrile （35： 65, adjusted pH to 6. 8 ）, the flow rate was 1.0 mL ·min^- 1, column temperature was 25 ℃, and the detection was set at 263 nm. Epidural 0. 5% levobupivacaine was administered as an anesthesia inducting agent at a bolus dose of 25.2± 1.1 mL in 30 healthy women （ ASA Ⅰ-Ⅱ）. The levobupivacaine concentration were measured by HPLC. Results：The linear range was 0. 025 - 1.0μg·mL^-1 ,r =0. 9998 and the limit of detection was 0. 01μg·mL^-1;The method recovery was 96. 1% - 102.8% （ n = 5 ）. Within - day precision（RSD） was 1.3% - 3.2% （ n = 5 ）, be- tween - day precision （RSD） was 3. 1% - 5.6 % （ n = 5 ）. The mean value in maternal venous blood （MV） was 0. 35 ± 0.24 μg·mL^-1 at the time of delivery. Levobupivacaine crossed the placental barrier with level in the umbilical vein blood（UV）of 0. 24 ± 0.21μg·mL^-1. The CUV/CMV was 0.72 ± 0. 34. Maternal concentration were always greater than umbilical venous concentrations at delivery. Conclusions：0. 5% levobupivacaine can cross the placental barrier quickly, and the dose have no apparent major adverse effects on the neonatal outcome.