Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Research Article

Analysis of Organic Components in Various Butyl Rubber Closures and their Compatibility Study with Cefamandole Nafate by HPLC/GC-MS

Author(s): Bingyong Xu, Jiarui Gao, Kaixian Tang, Fengmei Zhang, Shan Liu, Weike Su* and Jian Wang*

Volume 19, Issue 4, 2023

Published on: 27 February, 2023

Page: [330 - 344] Pages: 15

DOI: 10.2174/1573412919666230202153741

Price: $65

Abstract

Background: To control the quality of various butyl rubber closures and assess their applicability to cefamandole nafate, HPLC/ GC-MS methods were developed to qualitatively and quantitatively analyze the organic components in various types of butyl rubber closures and drug powder of cefamandole nafate for injection, and migration of these components from rubber closures to drug also were studied.

Materials and Methods: The chemical components in the rubber closures and corresponding drug were identified by GC-MS in full scan mode and NIST mass library. A GC-MS method in SIM mode was established to quantitatively analyze siloxane compounds, aromatic hydrocarbons and saturated chain-hydrocarbons in rubber closures and drugs. An HPLC method was established to quantitatively analyze antioxidants and sulfides from rubber closures and drugs. The turbidity values of powder for injection were measured by a turbidimeter. Further, the correlation between the content of organic components in the drug and the clarity of the solution was analyzed.

Results: It was found that the chemical components were released from butyl rubber closures and migrated to the drug, which influenced solution clarity of cefamandole nafate for injection and was the main factor to cause solution turbidity of powder for injection. The gradual migration of components occurred over time with the use of common butyl rubber closures, but the coated butyl rubber closures (rubber plated with membrane) were coated with a polytetrafluoroethylene film to block the contact between rubber closures and the drug, and could effectively prevent the migration of the components from rubber closures to drugs. The organic components in the butyl rubber closures were mainly identified as siloxanes, saturated chain-hydrocarbons, and antioxidants. An unknown ingredient was identified as 1-piperidinecarboxaldehyde, and trace amounts of toxic toluene were also detected within limits.

Conclusion: It is suggested that rubber plated with membrane or rubber closures of high quality were applicable to cefamandole nafate for injection and should be used in its production. HPLC/ GC-MS methods can be used as an effective method for quality control of butyl rubber closures and compatibility research with drugs to ensure drug safety for the public.

« Previous Next »
Graphical Abstract

[1]
Jenke, D.R. Linking extractables and leachables in container/closure applications. PDA J. Pharm. Sci. Technol., 2005, 59(4), 265-281.
[PMID: 16218205]
[2]
Richard. W. O. Jaehnke, Jorg Kreuter, and Gerard Ross. Interaction of robber closures with Powders for parenteral administration. J. Pharm. Sci. Technol., 1990, 44(5), 282-288.
[3]
Diane, M. Pasldet. Strategy for determining extractables from rubber packaging materials in drug products. J. Pharm. Sci. Technol., 1997, 51(6), 248-251.
[4]
Xiao, Q.Y.; Zhan, X.F.; Zhong, P. Study on compatibility of ceftriaxone sodium for injection. Acta Guangdong Colle Pharm., 2004, 20(6), 610.
[5]
Yan, Y.D.; Gu, H.M.; Hou, H.M. Elastomeric closures and quality of antibiotics for injection. Carol. J. Pharm., 2003, 34(4), 190.
[6]
Hun, J.; Wang, R.H. Study on compatibility of ceftriaxone sodium for injection. China Vent. Capi., 2016, 26, 382.
[7]
Zhao, X. Compatibility of medical butyl rubber plμg with ceftriaxone sodium Doctoral dissertation Peking Union Medical College: Beijing, 2018.
[8]
Guo, Y.J.; Li, W.C.; Yang, Q. Quality assessment of cefodizime sodium for injection. Chin. J. Antibiot., 2018, 43(3), 291.
[9]
Zhang, Fa Structural identification of extractables from rubber closures used for pre-filled semisolid applicator by chromatography, mass spectrometry and organic synthesis. J. Pharm. Biomed. Ana1., 2004, 34(5), 841-849.
[10]
Delaunay-Bertoncini, N.; van der Wielen, FW.; de Voogt, P. Analysis of low-molar-mass materials in commercial robber samples by Soxhlet and headspace extraction followed by GC-MS analysis. J. Pharm. Biomed. Anal., 2004, 35(5), 1059.
[11]
Zhao, X.; Hu, C.Q.; Jing, S.H. The analysis of volatile substances of butyl rubber closures. Yaowu Fenxi Zazhi, 2006, 26(3), 315.
[12]
Zhou, J.; Yin, G.; Liu, H.W. Determination of BHT in butyl rubber closures by GC-MS/MS. Carol. J. Pharm., 2013, 44(8), 801.
[13]
Liang, M.; Zou, Z.X.; Tang, X.; Ma, M.B.; Guo, J. Determination of dimethylcydosioxane residues in textiles by GC-MS. China Port Sci. Technol., 2020, 16(5), 33-42.
[14]
Hao, Y.H.; Wu, J.J. Determination of two siloxanes in silicone gel by GC-MS. Part B. Chem. Anal., 2015, 51, 818-820.
[15]
Li, Y.; Yang, H.Y.; Wang, F. Chin. Pharm. Aff., 2014, 28(11), 1257.
[16]
Jiang, Y.; Cheng, F.J. Determination of the antioxidant content and migration of the chlorinated butyl rubber plug with injection. Heilong Jiang Med. J., 2016, 29(3), 436.
[17]
Feng, J.; Cai, X.Y.; Liu, Y. Determination of antioxidant-BHT and vμlcanizing agent extractable sulfur in medicinal butyl rubber. Yaowu Fenxi Zazhi, 2017, 37(4), 702.
[18]
Chen, Z.S.; Liu, L.P. Study on the improvement of clarity and color in cefuroxime sodium for injection. Acad. J. Guangdong Coll. Pharm., 2010, 26(5), 459.
[19]
Chong, X.M.; Dong, X.; Yao, S.C.; Hu, C.Q. Research on the relationship between cephalosporin structure, solution clarity, and rubber closure compatibility using volatile components profile of butyl rubber closures. Drug Dev. Ind. Pharm., 2019, 45(1), 159.
[http://dx.doi.org/10.1080/03639045.2018.1526187] [PMID: 30231654]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy