不同脂质含量的脂肪乳对局部麻醉药物的吸附作用

Sorption of Local Anesthetics by Fat Emulsion with Different Content of Lipid

目的观察不同脂质含量的脂肪乳对局部麻醉药物的吸附效果,探讨脂肪乳救治局部麻醉药物中毒的机制。方法定量的盐酸布比卡因、盐酸罗哌卡因溶液中分别加入10%,20%,30%脂肪乳,漩涡10 min后,37℃下恒温水浴振荡15 h,离心后取下清液采用高效液相色谱(HPLC)检测。色谱柱为Agilent HC-C18(4.6 mm×250 mm,5μm),流动相为乙腈-10 mmol·L^(-1)磷酸二氢钠缓冲溶液(25∶75),用磷酸溶液调节p H值=3.5,流速1 m L·min^(-1),柱温30℃,检测波长210 nm。结果盐酸布比卡因在0.3~3.0μg·m L^(-1)浓度范围内线性关系良好,线性方程为Y=0.093 6X-0.017 3,r=0.999 6,最低检测限为0.05μg·m L^(-1)(S/N>3);盐酸罗哌卡因在0.3~3.0μg·m L^(-1)浓度范围内线性关系良好,线性方程为Y=0.086 6X-0.022 3,r=0.999 1,最低检测限为0.05μg·m L-1(S/N>3)。两种供试样品均在5 h内稳定,样品重复性良好。10%,20%,30%脂肪乳对等量盐酸布比卡因的吸附率分别为46.0%,70.4%,89.2%,对等量盐酸罗哌卡因的吸附率分别为51.3%,76.1%,90.7%。结论 10%,20%,30%脂肪乳电位、p H值相近,粒径略微增加,可以吸附游离盐酸布比卡因、盐酸罗哌卡因,且随着脂质含量的增加,其提取量增加。脂肪乳可提供脂质,使过量的或已经分布到组织的局部麻醉药物重新分散在油相中,从而降低局部麻醉药物毒性。

ObjectiveTo research sorption of local anesthetic by fat emulsion with different content of lipid in vitro and then to discuss the mechanism of action of fat emulsion for treatment of local anesthetic toxicity.Methods10%,20%,30%fat emulsion was added to the bupivacaine hydrochloride and ropivacaine hydrochloride.After the mixture was vortexed for10mins,it was vibrated in thermostatic water bath at37℃for15h,then centrifugated and got the aqueous phase to HPLC test.The chromatography was carried on a C18column(4.6mm×250mm,5μm),the mobile phase was composed of acetonitrile natrium biphosphoricum(25:75),the flow rate was1mL·min-1,the column temperature was30℃and the detection wavelength was set at210nm.ResultsUnder the condition of this test,the linear ranges and linear equations for bupivacaine hydrochloride and ropivacaine hydrochloride were0.3-3.0μg·mL-1,Y=0.0936X-0.0173(r=0.9996),and0.3-3.0μg·mL-1,Y=0.0866X-0.0223(r=0.9991)respectively.The lowest limit of quantitation were both0.05μg·mL-1(S/N>3),and the ingredients showed good relationships between the peak area and the concentration.Sample reproducibility was good because the test sample was stable in5h.The extraction rates of bupivacaine hydrochloride by10%,20%,30%fat emulsion were46.0%,70.4%,89.2%respectively.The extraction rates of ropivacaine hydrochloride by10%,20%,30%fat emulsion were51.3%,71.6%,90.7%respectively.ConclusionElectric potential and the pH value of the10%,20%,30%fat emulsion are similar,while the particle size increase slightly.Free bupivacaine hydrochloride and ropivacaine hydrochloride can be absorbed and with the increase of fat content,the extraction of local anesthetic is increased.The mechanism of action of fat for the treatment of local anesthetic toxicity maybe related to that fat emulsions can provided lipid,so that the excessive local anesthetic or those which had already distributesd in tissue can re dispersed in lipid,and then the plasma concentration of local anesthetic is reduced,the toxicity is also reduced.