Simultaneous Determination of 16 Substances in Medicinal Rubber Stoppers and Their Migration Amounts in Docetaxel Injection by GC-MS

WANG Xiaolan; REN Kun; JIANG Yan; ZHAO Daiguo; QI Yi; ZHANG Xiaoqian; LI Xi

doi:10.19554/j.cnki.1001-3563.2025.13.023

PDF(595 KB)

Packaging Engineering ›› 2025, Vol. 46 ›› Issue (13) : 205-213. DOI: 10.19554/j.cnki.1001-3563.2025.13.023

Simultaneous Determination of 16 Substances in Medicinal Rubber Stoppers and Their Migration Amounts in Docetaxel Injection by GC-MS

WANG Xiaolan, REN Kun, JIANG Yan, ZHAO Daiguo^*, QI Yi, ZHANG Xiaoqian, LI Xi

Author information +

History +

Abstract

The work aims to establish a gas chromatography-mass spectrometry (GC-MS) method to simultaneously investigate the extraction of 16 substances (2-ethylhexanol, 3 kinds of vulcanizing agents and 12 kinds of plasticizers) in medicinal rubber stoppers and their migration in docetaxel injection. A quantitative analysis was performed on a SH-Rxi-5 Sil MS capillary gas chromatography column (30 m×0.25 mm×0.25 μm) with a carrier gas flow rate of 1.2 mL/min and an electron impact ionization (EI) ion source. The most suitable pre-treatment method was determined by investigating the influence of extraction medium, time and mode on the effect of solid-liquid extraction. Good linear relationships were obtained in the concentration range of 30 ng/mL to 950 ng/mL , with correlation coefficients r≥0.995. The extraction recovery rates were 83.41% to 114.94%, and the relative standard deviations (RSD) were 1.07% to 4.93% (n=3). The migration recovery rates were 80.21% to 106.63%, and the RSDs were 0.63% to 3.63% (n=3). In conclusion, this method is simple to operate, highly specific, sensitive and efficient, and can be used for the extraction of 16 substances in medicinal rubber stoppers and the study of migration in docetaxel injection.

Key words

medicinal rubber stopper / gas chromatography-mass spectrometry / docetaxel injection / migration

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

WANG Xiaolan, REN Kun, JIANG Yan, ZHAO Daiguo, QI Yi, ZHANG Xiaoqian, LI Xi. Simultaneous Determination of 16 Substances in Medicinal Rubber Stoppers and Their Migration Amounts in Docetaxel Injection by GC-MS[J]. Packaging Engineering. 2025, 46(13): 205-213 https://doi.org/10.19554/j.cnki.1001-3563.2025.13.023

References

[1] 孟伟娟, 邱迎昕, 俞培富, 等. 我国药包材相关法规及卤化丁基药用胶塞与药物相容性分析方法研究进展[J]. 药物分析杂志, 2021, 41(11): 1860-1867.
MENG W J, QIU Y X, YU P F, et al.Regulations Relevant to Drug Packing Materials and Research Progress of Analytical Method of Drug Compatibility of Pharmaceutical Halobutyl Rubber Stoppers in Our Country[J]. Chinese Journal of Pharmaceutical Analysis, 2021, 41(11): 1860-1867.
[2] 薄晓文, 张敏, 郭利娟, 等. 气相色谱-质谱法测定药用丁基橡胶塞中18种多环芳烃的含量[J]. 分析科学学报, 2021, 37(5): 680-685.
BO X W, ZHANG M, GUO L J, et al.Determination of Eighteen Polycyclic Aromatic Hydrocarbons in Pharmaceutical Butyl Rubber Closures by GC-MS[J]. Journal of Analytical Science, 2021, 37(5): 680-685.
[3] 张罗红, 黄婉莎, 张欣, 等. 药用橡胶塞中17种多环芳烃测定方法[J]. 包装工程, 2021, 42(17): 10-19.
ZHANG L H, HUANG W S, ZHANG X, et al.Determination Methodology of 17 Polycyclic Aromatic Hydrocarbons in Pharmaceutical Rubber Stoppers[J]. Packaging Engineering, 2021, 42(17): 10-19.
[4] 罗露露, 王子杏, 郭栋, 等. GC-MS/MS法测定药用溴化丁基胶塞中的浸出物[J]. 今日药学, 2023, 33(2): 123-127.
LUO L L, WANG Z X, GUO D, et al.Determination of Extractables from Medicinal Bromobutyl Rubber Stoppers through Gas Chromatography-Tandem Mass Spectrometry[J]. Pharmacy Today, 2023, 33(2): 123-127.
[5] 成婕, 张罗红, 江燕, 等. 药用胶塞常用抗氧剂及可提取硫含量测定方法[J]. 包装工程, 2023, 44(3): 80-86.
CHENG J, ZHANG L H, JIANG Y, et al.Determination of Antioxidants and Extractable Sulfur in Medicinal Rubber Stopper[J]. Packaging Engineering, 2023, 44(3): 80-86.
[6] FASIHNIA S H, PEIGHAMBARDOUST S H, PEIGHAMBARDOUST S J, et al.Migration Analysis, Antioxidant, and Mechanical Characterization of Polypropylene-Based Active Food Packaging Films Loaded with BHA, BHT, and TBHQ[J]. Journal of Food Science, 2020, 85(8): 2317-2328.
[7] 李立根, 吴莹, 张毅兰. 药用胶塞硫化剂对叔辛基苯酚甲醛树脂中对叔辛基苯酚的测定[J]. 中国医药工业杂志, 2016, 47(5): 614-617.
LI L G, WU Y, ZHANG Y L.Determination of Octylphenol from Octyl-Phenolic Curing Resin in Rubber Stoppers for Pharmaceutical Use[J]. Chinese Journal of Pharmaceuticals, 2016, 47(5): 614-617.
[8] 李美玲, 卢秀芳, 刘文枚, 等. 气相色谱-质谱联用法测定药用胶塞中对特辛基苯酚含量[J]. 中国药业, 2024, 33(24): 93-96.
LI M L, LU X F, LIU W M, et al.Determination of P-Tert-Octylphenol in Medicinal Rubber Stoppers by GC-MS[J]. China Pharmaceuticals, 2024, 33(24): 93-96.
[9] 王芳, 朱旭, 刘超栋. 硫化剂辛基酚醛树脂对热塑性溴化丁基橡胶/聚丙烯动态硫化弹性体性能的影响[J]. 塑料工业, 2018, 46(3): 109-113.
WANG F, ZHU X, LIU C D.Effect of Curing Agent Octyl Phenolic Resin Amount on the Properties of Thermoplastic BIIR/PP Dynamic Vulcanized Rubber[J]. China Plastics Industry, 2018, 46(3): 109-113.
[10] 昝艳楠, 张晓芸, 商少华, 等. 液液萃取/气相色谱-质谱法测定氟[18F]脱氧葡糖注射液塑料生产组件浸提液中16种邻苯二甲酸酯类增塑剂[J]. 分析测试学报, 2023, 42(3): 357-362.
ZAN Y N, ZHANG X Y, SHANG S H, et al.Liquid-Liquid Extraction/Gas Chromatography-Mass Spectrometry Determination of 16 Kinds of Phthalate Plasticizers in the Extract of Fluorine [18F] Deoxyglucose Injection Plastic Production Module[J]. Journal of Instrumental Analysis, 2023, 42(3): 357-362.
[11] 贺诗意, 张蕊, 周明慧, 等. 植物油中邻苯二甲酸酯类塑化剂检测技术研究现状[J/OL]. 中国油脂, 2024: 1-12 (2024-08-13). https://link.cnki.net/doi/10.19902/j.cnki.zgyz.1003-7969.230534.
HE S Y, ZHANG R, ZHOU M H, et al. Current Status of Research on Detection Techniques for Phthalate Esters(PAEs) Plasticizer in Vegetable Oil[J/OL]. China Oils and Fats, 2024: 1-12 (2024-08-13). https://link.cnki.net/doi/10.19902/j.cnki.zgyz.1003-7969.230534.
[12] 王林啸, 高珂, 李建佳, 等. 基于全二维气相色谱-飞行时间质谱分析室内灰尘中邻苯二甲酸酯及其新型替代品[J]. 色谱, 2025, 43(2): 185-196.
WANG L X, GAO K, LI J J, et al.Analysis of Phthalate Esters and Their Novel Alternatives in Indoor Dust Using Comprehensive Two-Dimensional Gas Chromatography-Time of Flight Mass Spectrometry[J]. Chinese Journal of Chromatography, 2025, 43(2): 185-196.
[13] 赵继芳. 偏苯三甲酸酐与2-乙基己醇非酸催化酯化合成偏苯三甲酸三(2-乙基己)酯[J]. 石油化工, 1993, 22(7): 461-465.
ZHAO J F.Synthesis of Tri(2-Ethylhexyl)Trimellitate from Trimellitic Anhydride and 2-Ethylhexanol by Esterification with Nonacid Catalyst[J]. Petrochemical Technology, 1993, 22(7): 461-465.
[14] 张薇. 邻苯二甲酸二辛酯生产工艺评述[J]. 湖南化工, 1998, 28(6): 7-8.
ZHANG W.A Review on the Production Technology of Di (2 Ethyl Hexyl) Phthalate[J]. Fine Chemical Intermediates, 1998, 28(6): 7-8.
[15] 张文华, 吉丽娜, 冯靖, 等. 药包材相容性研究中邻苯二甲酸酯类增塑剂的安全性评估[J]. 中国药学杂志, 2023, 58(6): 533-536.
ZHANG W H, JI L N, FENG J, et al.Assessing Safety of Phthalate in the Compatibility Study between Pharmaceutical Packing Materials and Drugs[J]. Chinese Pharmaceutical Journal, 2023, 58(6): 533-536.
[16] 王笑妍, 薛燕波, 者东梅, 等. 邻苯二甲酸酯类增塑剂概况及法规标准现状[J]. 中国塑料, 2019, 33(6): 95-105.
WANG X Y, XUE Y B, ZHE D M, et al.Overview of Phthalate Plasticizers, Current Regulations and Standards[J]. China Plastics, 2019, 33(6): 95-105.
[17] 王金鹏, 孙国祥. 以TOTM增塑的PVC输液器的药物相容性研究[J]. 中国医药工业杂志, 2024, 55(9): 1263-1270.
WANG J P, SUN G X.Drug Compatibility of PVC Infusion Sets Plasticized with TOTM[J]. Chinese Journal of Pharmaceuticals, 2024, 55(9): 1263-1270.
[18] 李樾, 孙会敏. 药用卤化丁基胶塞中硫化剂及抗氧剂的HPLC法测定[J]. 中国医药工业杂志, 2021, 52(10): 1377-1381.
LI Y, SUN H M.Determination of Vulcanizing Agent and Antioxidant in Halogenated Butyl Rubber Stoppers by HPLC[J]. Chinese Journal of Pharmaceuticals, 2021, 52(10): 1377-1381.
[19] 梁波, 郑烨, 王蓉佳, 等. 顶空气相色谱法研究一次性输液器中环己酮和2-乙基己醇的迁移[J]. 中国医药工业杂志, 2021, 52(2): 250-253.
LIANG B, ZHENG Y, WANG R J, et al.Migration of Cyclohexanone and 2-Ethyl-1-Hexanol in Disposable Infusion Sets Determined by Headspace Gas Chromatography[J]. Chinese Journal of Pharmaceuticals, 2021, 52(2): 250-253.