气相色谱法测定一次性PVC插管增塑剂ATBC在全血中的溶出

目的：在临床条件与极限条件下，建立气相色谱法（GC法）测定一次性使用动（静）脉插管增塑剂乙酰柠檬酸三正丁酯（ATBC）在全血中以及乙醇-水（密度0.937 3~0.937 8 g&#183;cm^-3）中的溶出量，为该产品的安全性评价提供依据。方法：采用正己烷萃取血液样品中的ATBC以及真空干燥法提取乙醇水中的ATBC，以GC法测定ATBC的含量。其中采用气相色谱柱为Hp-5MS （30 m&#215;0.25 m&#215;0.25 μm，美国安捷伦），进样量2 μL，进样温度250℃，分流比1：1，载体流速5 mL&#183;min^-1，升温程序：初始温度75℃，保持1 min，按15℃&#183;min^-1速率升至270℃，保持2 min。并对测定方法进行方法学研究。结果：GC方法测定ATBC质量浓度在5.14~102.8 μg&#183;mL^-1范围内线性关系良好（r=0.999 7），检测限为1.067 ng，仪器精密度RSD<5%；正已烷萃取法的回收率为（75.1&#177;4.10）%，真空干燥萃取法的回收率为（70.5&#177;2.40）%。在临床条件（2 L&#183;min^-1，循环4 h）下，一次性动静脉插管在全血中增塑剂ATBC的溶出量为（26.96 &#177;2.18） mg&#183;套^-1，在乙醇水中的溶出量为（30.94&#177;0.98） mg&#183;套^-1；在极限条件（6 L&#183;min^-1，循环4 h）下，一次性动静脉插管在全血中增塑剂ATBC的溶出量为（15.74 &#177;2.50） mg&#183;套^-1，在乙醇水中的溶出量为（25.71&#177;0.30） mg&#183;套^-1。结论：本法经方法学验证，可以用于测定ATBC在全血以及乙醇水中的溶出量，并且发现在相同的浸提介质中，浸提介质的循环速度越快，增塑剂ATBC的溶出量越低，同时在相同浸提条件下，增塑剂ATBC在乙醇水（密度0.937 3~0.937 8 g&#183;cm^-3）中的溶出量高于全血中的ATBC溶出量。

Objective: was establish gas chromagraphy(GC)method for determination of acetyl tributyl citrate(ATBC)released from disposable arterial(intravenous)cannula into fresh blood and ethanol/water with density from 0.937 3 to 0.937 8 g&#183;cm^-3,and provide a basis for safety evaluation of the kind of products.Methods: ATBC in the whole blood was extracted by n-hexane and ATBC in the ethanol/water was obtained by vacuum drying method,and the quantification of ATBC was achieved by GC.The GC capillary column was an HP-5MS(30 m&#215;0.25 mm&#215;0.25 μm,Agilent Technologies),2 μL was injected by needle at injector temperature of 250℃ using split model(1:1),and the flow rate of carrier gas(high purity nifrogen)for column was 25 mL&#183; min-1.Temperacture program for column:75℃for 1 min,at 15℃&#183;min^-1 to 270℃remaining 2 min.The determination was verified by methodology study.Results: The data on the methodology study of GC was presented that the calibration curves of ATBC had a good linear relationship(r=0.999 7)in the concentration range of 5.14-102.8 μg&#183;mL^-1,the detection limit was 1.067 ng,instrumental precision showed RSD < 5%.The recovery rate of n-hexane extraction was(75.1&#177;4.1)% and the recovery rate of vacuum drying method was(70.5&#177;2.4)%.Under the recommended clinical conditions(2 L&#183;min^-1,circulating 4 hours),the amount of ATBC released into whole blood was(26.96 &#177;2.18) mg per set and amount into ethanol/water was(30.94&#177;0.98) mg per set;under the limited clinical conditions(6 L&#183;min^-1, circulating 4 hours),the amount of ATBC released into whole blood was (15.74 &#177;2.50) mg per set and amount into ethanol/water was(25.71&#177;0.30) mg per set.Conclusion: This method was valid for determination of ATBC released into whole blood and ethanol/water,and it was found that the released amount of ATBC was increasing with decreased circulation velocity by using the same medium,and the ATBC had a higher migration into ethanol water(density from 0.937 3 to 0.937 8 g&#183;cm^-3)than that into whole blood at the same extraction conditions.