乌头碱在家兔体内的代谢动力学初步研究

本文应用甲醇-0.05mol/L碳酸铵水溶液-二氯甲烷(90:10:2)作流动相,在YWGC_(18)H_(37)反相键合相色谱柱上分离乌头碱和内标,用紫外分光检测器在235nm外定量,改进了动物组织内痕量乌头碱的HPLC检测法。运用该法检测家兔静脉注射乌头碱后的血毒物浓度,初步研究了乌头碱在家兔体内的代谢动力学过程,表明其体内过程符合开放二室模型,T_(1/2α)=1.4682min,T_(1/2β)=34.1379min。体内乌头碱可以原形由尿和胆汁中排出,但以前6h尿排泄为主。

TOXICOKINETIC STUDIES OF ACONITINE IN RABBITS

A high performance liquid chromatographic method has been improved for determination of aconitine in rabbit blood using a reversed phase chromatographic column (YWG-C_(18)H_(37),10μm) and a precolumn(Micro-pak, 5μm, 40×4mm I.D.), with tetracaine as internal standard and methanal-0.05mol/L ammonium carb onate-dichlormethane(90:10:2) as mobile phase. It is more simple, more precise, more specific, more rapid and ecnomical than other assays using in forensic toxicological poison analysis at present. The procedure is as follows: Take 2 mL of rabbit blood, add 20 μL of the internal standard (50μg/mL), 5 mL of ether and TmL of ammonia(2.5%). Shake for 10 minutes and centrifuge for 10 minutes at 5000r/min. The residue is extracted with the same ammount fresh ether for two times as above. The combination of ether which is taken out three times is mixed with 1 mL of 0.1 N hydrochloric acid. Evaporate the ether to 5 mL at 40℃ and under nitrogen gas flow, then draw the remaining ether out. Mix the acid phase with 1 mL of dichlormethane and 1 mL of ammonia (2.5%), centrifuge for 5 minutes. Take the upper layer out and evaporate the lower in the changed KD enrichment installation to dryness at 40℃ under nitrogen gas flow and lower preesure. Reconstitute the residue with 100μL of methanol and inject 40μL into the chromatograph. The mean recovery of aconitine was 96.75% and coefficient variation was 5.49%. The method was liner from 0.1 to 5.0μg/2mL with correlation coefficient of 0.9992. Toxicokinetics of aconitine was studied with HPLC as above in 10 rabbits after intravenous injection at a dose of 0.06mg/kg. The results showed that the curve of the logarithm of the concentration of aconitine in blood versus time fitted well to a two compartment model. The following toxicokinetic parameters were obtained: T1/2α 1.4682min, T1/2β 34.1379min, K_(12) 0.2418min~(-1), K_(21) 0.2035 min~(-1), V_1 31.6012 mL/kg, V_2 41.7181 mL/kg, Cl 1.4885 mL/min. Elimination of aconitine from rabbit was mainly in urine and within 6 hours after injection.