Objective: To extract 4,4’-diaminodiphenyl methane (MDA) in hemodialyzer by exhaustive extraction, and to establish an HPLC method for determination of MDA releaseand its allowable limits (AL). Methods: MDA was extracted from hemodialyzer using methanol-water(1∶1) and methanol respectively. The Sun Fire C18(4.6 mm×250 mm, 5 μm) column was used to determine the optimal detection wavelength with a photo-diode array (PDA) detector. Injection volume was 10 μL and the mobile phase was methanol, phosphate buffer and deionized water. Gradient elution at the flow rate of 1.0 mL·min-1was applied. Column temperature was 40 ℃. Results: For methanol-water(1∶1), the optimal detection wavelength was 242 nm, the calibration curves of MDA had a good linear relationship (r2=0.999 8) in the concentration range of 0-2.03 μg·mL-1. The limit of quantification was 0.081 μg·mL-1, instrument precision and recovery rate were excellent and the result of MDA release was 59.7 μg. For methanol, the optimal detection wavelength was 240 nm, the calibration curves of MDA had a good linear relationship (r2=0.999 7) in the concentration range of 0-2.04 μg·mL-1, the limit of quantification was 0.067 μg·mL-1,the instrument precision was good, but the recovery rate was relatively low.The result of MDA release was 64.1 μg. The AL of MDA release in hemodialyzer was 0.105 mg·d-1. Conclusion: This method is validated for determination of MDA release in hemodialyzer, but methanol-water (1∶1) is not suitable for the exhaustive extraction with low MDA concentration. Methanol extract can be concentrated by nitrogen blowing to complete the exhaustive extraction.
SUN Jin-lu, FANG Jing-yi, WANG Ling-ling, WANG Ying-ying, LI Feng, ZHANG Jing-jing
. Determination of 4,4’-diaminodiphenyl methane released in hemodialyzer and establishment of allowable limits[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(9)
: 1618
-1624
.
DOI: 10.16155/j.0254-1793.2022.09.15
[1] 陶雪,王洪伟,杜欢永,等.血浆中二苯基甲烷二胺的气相色谱-质谱测定法[J].中华劳动卫生职业病杂志, 2006,24(1):47
TAO X, WANG HW, DU HY, et al. Determination of diphenylmethane diamine in plasma by gas chromatography-mass spectrometry[J].Chin J Ind Hyg Occup Dis, 2006, 24(1):47
[2] MARTELLI A, CARROZZINO R, MATTIOLI F, et al. DNA damage induced by 4,4’-methylenedianiline in primary cultures of hepatovytes and thyre-ocytes from rats and humans[J].Toxicol Appl Pharmacol, 2002,182(3):219
[3] European Commission-Join Research Centre, Institute for Health and Consumer Protection, European Chemicals Bureau (ECB). European Union Risk Assessment Report: 4,4’-methylenedianiline (MDA) [DB/OL]. Series: 1rd Priority List, Volume 9, Final report 2001. https://echa.europa.eu/documents/10162/ba567fa3-282c-4b37-bcba-f82fd9ae52bc
[4] KENYON SH, BHATTACHARYYA J, BENSON CJ, et al. Percutaneous penetration and genotoxicity of 4,4’-methylenedianiline through rat and human skin in vitro[J].Toxicology, 2004, 196(1-2):65
[5] BOLOGNESI C, BAUR X, MARCZYNSKI B, et al. Carcinogenic risk of toluene diisocyanate and 4,4’-methylenediphenyl diisocyanate and epidemiological and experimental evidence[J].Crit Rev Toxicol, 2001, 31(6):737
[6] 黄元礼,孙雪,柯林楠,等.血液透析导管中残留单体二苯甲烷二异氰酸酯的检测[J].中国组织工程研究,2018,22(6):927
HUANG YL, SUN X, KE LN, et al. Detection of residual diphenylmethane diisocyanate monomer in a hemodialysis catheter[J].Chin J Tissue Engin Res, 2018, 22(6):927
[7] 王翔,王祖兵,赵忠林.工作场所空气中二苯基甲烷二异氰酸酯浸渍滤纸采集-高效液相色谱法[J].中华劳动卫生职业病杂志,2019,37(5):389
WANG X, WANG ZB, ZHAO ZL. Determination of diphenylmethane diisocyanate in workplace air by HPLC with impregnated filter membrane[J].Chin J Ind Hyg Occup Dis, 2019, 37(5):389
[8] 王景春,严志宏,王昊.静脉留置针中MDI溶出测定及安全性评价[J].中国医疗器械信息,2018,24(21):36
WANG JC, YAN ZH, WANGH. MDI dissolution determination and safety evaluation in intravenous indwelling needle[J].China Med Dev Inf, 2018, 24(21):36
[9] YY/T 1639-2018 一次性使用聚氨酯输注器具二苯甲烷二异氰酸酯(MDI)残留量测定方法[S].2018
YY/T 1639-2018.Determination of Residual of Diphenylmethane Diisocyanate (MDI) from Thermoplastic Polyurethane Infusion Equipments for Single Use[S].2018
[10] ISO 10993-18:2020. Biological Evaluation of Medical Devices—Part 18: Chemical Characterization of Medical Device Materials within a Risk Management Process[S].2020
[11] MADER PM. Hydrolysis kinetics for p-dimethylaminophenylisocyanate in aqueous solutions[J].J Org Chem, 1968, 33(6):2253
[12] 范丽静,徐苏华,颜林,等.血液透析器中4,4’-甲基二苯基二异氰酸酯残余量的思考[J].临床医学工程,2019,12(26):23
FAN LJ, XU SH, YAN L, et al. Reflection on residual amount of 4,4’-methyldiphenyl diisocyanate in hemodialyzer[J].Clin Med Eng, 2019, 12(26):23
[13] 陈冬梅,张玉冰. NMR对MDI在稀溶液中水解反应机理的表征[J].分析测试学报, 2009,28(7):849
CHEN DM, ZHANG YB. Characterization of hydrolyzing of diphenylmethane diisocyanate in dilute solution by NMR[J].J Instrum Anal, 2009, 28(7):849
[14] 潘雪峰.室温下异氰酸酯与水反应动力学的研究[D].沈阳:东北林业大学, 2003
PAN XF. The Reaction Kinetics of Isocyanate with Water Is Undertaking in Room Temperature[D].Shenyang:Northeast Forestry University, 2003
[15] ISO 10993-12:2021. Biological Evaluation of Medical Devices—Part 12: SamplePreparation and Reference Materials[S].2021
[16] 叶成红,邓洁,肖丽,等.医疗器械可沥滤物安全性研究(Ⅱ):残留量检测[J].中国药事, 2019,10(33):1116
YE CH, DENG J, XIAO L, et al. Safety study of leachable substances of medical device (Ⅱ):residue detection[J].Chin Pharm Aff, 2019, 10(33):1116
[17] ISO 10993-1:2018. Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing Within a Risk Management Process[S].2018
[18] ISO 10993-17:2002. Biological Evaluation of Medical Devices—Part 17: Establishmentof Allowable Limits for Leachable Substances [S].2002
