Objective: To improve gas chromatographic (GC) method for the determination of palmitic acid and stearic acid, and to establish a non-derivative GC method for determining the extracted amount and migration amount of palmitic acid and stearic acid in medicinal rubber stopper. Methods: A DB-FFAP capillary column (30 m×0.25 mm, 0.25 μm) was used and column temperature was programmed heating up. The initial temperature was kept at 100 ℃ for 1min, then the temperature was raised to 230 ℃ at the rate of 60 ℃·min-1 and kept for 20 min. The inlet temperature was 250 ℃, FID detector temperature was 250 ℃, the split ratio was 10∶1 and the carrier gas flow rate was 1.0 mL·min-1. Results: The linear ranges of palmitic acid stearic acid were 0.884 4-88.44 μg·mL-1 (r2=0.999 9) and 1.234-123.4 μg·mL-1(r2=0.999 8), respectively, and the lower limit of detection were 0.442 and 0.617 μg·mL-1, respectively, with the recoveries of 96.5% and 91.3%, respectively. The content of palmitic acid and stearic acid in rubber plug was 0.019% and 0.020%, respectively, and the migration of palmitic acid and stearic acid in medicine was lower than the safety threshold. Conclusion: The sample pretreatment is simple, efficient, rapid and dispense with lots of dangerous and toxic reagents. The method is sensitive and accurate with good repeatability. The validation results show that the method can be used to determine the migration of palmitic acid and stearic acid from rubber stopper to ceftizoxime sodium for injection.
HAN Hai-yan, WU Hong-yang, ZHANG Pu, LI Sha, CAO Xi, ZHANG Fan, FAN Neng-quan
. An improved method for the determination of free palmitic acid and stearic acid in medical rubber stopper by GC[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(11)
: 2024
-2030
.
DOI: 10.16155/j.0254-1793.2021.11.21
[1] 李立根, 张毅兰. 药用胶塞及其与药品的相容性简述[J].中国医药工业杂志, 2015, 46(12):1366
LI LG, ZHANG YL. Review of rubber stoppers for pharmaceuticaluse and its compatibility with pharmaceutical products [J].Chin J Pharm, 2015, 46(12):1366
[2] 薛转茹. 药用卤化丁基胶塞相容性研究[J].海峡药学, 2017, 29(7):8
XUE ZR. Research on the compatibility of medical grade halogenated butyl rubber stopper[J].Strait Pharm J, 2017, 29(7):8
[3] 尹翔, 霍东风, 仲昭庆.气相色谱法测定卤化丁基胶塞中棕榈酸和硬脂酸的含量[J].黑龙江医药, 2018, 31(5):949
YIN X, HUO DF, ZHONG ZQ. Determination of palmitic acid and stearic acid in halogenated butyl rubber stopper with GC method[J].Heilongjiang Med J, 2018, 31(5):949
[4] 覃济桓, 张兆佳, 王海燕. 注射用血栓通(冻干)与氯化丁基胶塞相容性研究中抗氧剂的含量测定[J].大众科技, 2020, 22(250):32
TAN JH, ZHANG ZJ, WANG HY. Determination of antioxidants in the study of compatibility between xueshuantong for injection (lyophilized) and chlorinated butyl rubber plugs[J].Popul Sci Technol, 2020, 22(250):32
[5] 谢兰桂,赵霞,王峰,等.药用卤化丁基胶塞中脂肪酸类物质含量的测定[J].塑料科技, 2014, 42(9):102
XIE LG, ZHAO X, WANG F, et al. Determination of fatty acids in rubber stoppers[J].Plast Technol, 2014, 42(9):102
[6] 蒲小聪, 陈蕊, 游延军. HPLC法测定胶塞中抗氧剂1076向米卡芬净钠注射液中的迁移[J].药物分析杂志, 2017, 37(7):1298
PU XC, CHEN R, YOU YJ. HPLC determination for migration of antioxidant 1076 from rubber stopper to micafungin sodium injection[J].Chin J Pharm Anal, 2017, 37(7):1298
[7] 魏雪峰, 宋大龙, 苏俊杰,等. 硬脂酸用量对天然橡胶性能的影响机理分析[J].弹性体, 2018, 28(6):6
WEI XF, SONG DL, SU JJ, et al. Efcet of amount of stearic acid on properrties of natural rubber[J].China Elastom,2018, 28(6):6
[8] 赵霞,胡昌勤,金少鸿. 药用丁基胶塞中易挥发性成分的成分分析[J].药物分析杂志, 2006, 26(3):315
ZHAO X, HU CQ, JIN SH. The analysis of volatile subsatnces of buytl rubber closures[J].Chin J Pharm Anal, 2006,26(3):315
[9] 冯晓, 宋国新, 胡耀铭. GC-MS法测定亚麻籽中脂肪酸含量[J].实验技术与管理, 2011, 28(11):278
FENG X, SONG GX, HU YM. Determination of fatty acid content in flax seed by GC/MS[J].Exp Technol Manag, 2011, 28(11):278
[10] 曾建立, 杜泽学, 陈艳凤. 气相色谱分析未衍生化脂肪酸及其甲酯[J].石油炼制与化工, 2012, 43(7):104
ZENG JL, DU ZX, CHEN YF. Underived fatty acids and methyl esters were analyzed by gas chromate graphy[J].Petrol Process Gandptrochem, 2012, 43(7):104
[11] 刘颖沙, 崔利辉, 赵璐,等. 植物油中脂肪酸的气相色谱法测定[J].湖北农业科学, 2020, 59(8):129
LIU YS, CUI LH, ZHAO L, et al. Determination of fatty acids in vegetable oil by gas chromatography[J].Hubei Agric Sci, 2020, 59(8):129
[12] 刘佩珊, 牟燕, 马安德,等. 气相色谱-质谱法测定血浆中31 种游离脂肪酸含量[J].分析测试学报, 2020, 39(8):1000
LIU PS, MOU Y, MA AD, et al. Determination of 31 free fatty acids in plasma by gas chromatography-mass spectrometry[J].J Instrum Anal, 2020, 39(8):1000
[13] 孟哲, 文大为, 廖一平,等. 快速气相色谱法测定食用油中的未衍生化长链脂肪酸[J].色谱, 2007, 25(2):254
MENG Z, WEN DW, LIAO YP, et al. Determination of underivatized long-chain fatty acids in edible oils by fast gas chromatography[J].Chin J Chromatogr, 2007, 25(2):254
[14] 陈满姑. 气相色谱检测食品中反式脂肪酸的方法研究[J]. 现代食品, 2020,3(21):215
CHEN MG. Study on the method of detecting trans fatty acids in food by gas chromatography[J].Mod Food, 2020,3(21):215
[15] EP 9.0. <3.1.6> Polyproplene for Containers for Parenteral Preparations and for Ophthalmic Preparations [S]. 2017:403
[16] USP 40-NF 35. <729> Globular Size Distribution in Lipid Injectable Emulsions[S]. 2016:607
