Objective: To establish a GC-FID method to determine the content of 17 phthalic ester plasticizers in adsorbed tetanus vaccine. Methods: The protein was precipitated with acetonitrile, and the layers were separated by salting out with sodium chloride. The supernatant was transferred and analyzed by GC-FID with external standard method. Agilent HP-5 (30 m×0.32 mm×0.25 μm) capillary column was adopted. The temperature program: Initial temperature of 50 ℃ was maintained for 1 min, then was increased to 230 ℃ at the rate of 20 ℃·min-1 and was maintained for 3 min. The temperature was increased to 300 ℃ at a rate of 5 ℃·min-1 and maintained for 5 minutes. Column flow rate was 1 mL·min-1. The temperatures of detector and inlet were 280 ℃ and 250 ℃ respectively. The linear velocity of the carrier gas (nitrogen) was set to 19.148 cm·s-1. The injection volume was 1 μL and the split mode was splitless. The sampling mode: automatic injection. Results: The 17 plasticizers showed good linear relationship in the range of 0.5-20 μg·mL-1 with a correlation coefficient more than 0.99. At three different concentrations (15, 10, 5 μg·mL-1) of spiked samples, the recovery rates of 17 plasticizers ranged from 83.6% to 111.2%, with RSD between 0.39% and 3.9%. No plasticizers were detected in 5 batches of adsorbed tetanus vaccine by this method. Conclusion: The method has good specificity, high accuracy and precision, good solution stability, and high durability. It can be used to determine contents of plasticizers in adsorbed tetanus vaccine drugs.
GAO Yan, LU Ze-hua, ZHI Qi-hang, TIAN Wen-di, WANG Li, SHEN Zhi-qiang, WANG Bin
. Determination of 17 phthalate plasticizers in adsorbed tetanus vaccine by gas chromatography[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(3)
: 463
-471
.
DOI: 10.16155/j.0254-1793.2023.03.13
[1] 张虹. 邻苯二甲酸二(2-乙基)己酯和偏苯三酸三辛酯在临床不同药液中溶出量的比较[J].色谱, 2015, 33(5):522
ZHANG H. Comparison of the release behaviors of di(2-ethylhexyl) phthalate and tri(2-ethylhexyl)trimellitate from the polyvinyl-chloride infusion set into pharmaceutical solutions[J].Chin J Chromatogr, 2015, 33(5):522
[2] 王婷, 高星梅, 郭会彩, 等. 增塑剂DEHP神经毒性作用及机制的研究进展[J].生态毒理学报, 2022, 17(2):33
WANG T, GAO XM, GUO HC, et al. Research progress on neurotoxic effects and mechanism of plasticizer DEHP[J].Asian J Ecotoxicol, 2022, 17(2):33
[3] 胡希俅. DEHP增塑剂应用于聚氯乙烯医疗器械中的安全性分析[J].塑料助剂, 2021, 2: 59
HU XQ. Safety analysis of DEHP plasticizer used in PVC medical devices[J].Plastics Addit, 2021, 2: 59
[4] PASQUALE V, DOMENICA V, EMILIO R, et al. Phthalates: european regulation, chemistry pharmaco kinetic and related toxicity[J].Envir Toxicol Pharmacol, 2013, 36(1):88
[5] 刘晓毅, 蒋可新, 石维妮. 国内外食品接触材料中邻苯二甲酸酯类塑化剂迁移限量对比分析[J].食品工业科技, 2011, 32(10):397
LIU XY, JIANG KX, SHI WN. Comparative analysis of specific migration limits of phthalate plasticizer in food contact materials[J].Sci Technol Food Ind, 2011, 32(10):397
[6] 黄婵媛, 蔡玮红, 莫锡乾. 邻苯二甲酸酯类的特性及在食品中的限量分析[J].包装与食品机械, 2014,32(2):66
HUANG CY, CAI WH, MO XQ. The toxicity and limited provisions of phthalate esters in food[J].Pack Food Machin, 2014, 32(2):66
[7] 化学药品注射剂与药用玻璃包装容器相容性研究技术指导原则(试行)[S].2015: 1
Technical Guidelines for Compatibility Study between Chemical Injection and Medicinal Glass Packaging Container (Trial)[S].2015: 1
[8] 化学药品注射剂与塑料包装材料相容性研究技术指导原则(试行)[S].2012: 1
Technical Guidelines for Compatibility Study between Chemical Injection and Plastic Packaging Materials (Trial) [S].2012: 1
[9] 化学药品与弹性体密封件相容性研究技术指导原则(试行)[S].2018: 1
Technical Guidelines for Compatibility Research between Chemicals and Elastomer Seals (Trial)[S].2018: 1
[10] FDA: Container Closure Systems for Packaging Human Drugs and Biologics[S].1999: 1
[11] EMEA: Guidance on Plastic Immediate Packaging Materials[S].2005: 1
[12] 张广湘. 重组人促红素注射液与预灌封注射器相容性研究[D].广州: 华南理工大学, 2016
ZHANG GX. Compatibility Studies on Recombinant Human Erythropoietin Injection with Prefillable Syringes[D].Guangzhou: South China University of Technology, 2016
[13] NATALIA N, KATELL F, KONI G, et al. Contamination of vegetable oils marketed in Italy by phthalic acid esters[J].Food Control, 2011, 22(2):209
[14] 张璇, 陈大舟, 汤桦, 等. 顶空固相微萃取/气相色谱-质谱法测定液态化妆品中8种增塑剂[J].分析测试学报, 2012, 31(3):317
ZHANG X, CHEN DZ, TANG H, et al. Determination of 8 phthalate esters in liquid cosmetics using solid-phase microextraction/gas chromatography-mass spectrometry[J].J Instrum Anal, 2012, 31(3):317
[15] SALAZAR-BELTRÁN D, HINOJOSA-REYES L, RUIZ-RUIZ E, et al. Determination of phthalates in bottled water by automated on-line solid phase extraction coupled to liquid chromatography with uv detection[J].Talanta, 2017, 168: 291
[16] 赵世文, 林佶, 孙灿, 等. 液相色谱-质谱/质谱双柱法直接测定白酒中15种邻苯二甲酸酯[J].中国卫生检验杂志, 2013, 23(16):3192
ZHAO SW, LIN Z, SUN C, et al. Determination of 15 phthalates in liquor by double-column liquid chromatography tandem mass spectrometry[J].Chin J Health Lab Technol, 2013, 23(16):3192
[17] MARÍA CBA, NEREA OL, PILAR BB. Solid phase extraction using molecular imprinted polymers for phthalate determination in water and wines samples by HPLC-ESI-MS[J].J Microchem, 2017(132):233
[18] 马康, 汤福寿, 何雅娟,等. 食品包装材料中13种增塑剂的毛细管气相色谱法测定[J].分析测试学报, 2011, 30(3):284
MA K, TANG FS, HE YJ, et al. Determination of thirteen plasticizers in food plastic packaging materials by capillary column gas chromatography[J].J Instrum Anal, 2011, 30(3):284
[19] 杨瑛, 樊文娟. GC-FID法测定塑料包材中16种邻苯二甲酸酯类化合物[J].食品科学, 2013, 34(20):250-254
YANG Y, FAN WJ. Determination of 16 kinds of phthalate esters in plastic food packaging materials by GC-FID[J].Food Science, 2013, 34(20):250
