Objective: To establish a method for the determination of tacrolimus and pimeclimus in cosmetics by high performance liquid chromatography with a triple quadruple tandem mass spectrometry (HPLC-MS/MS), and was used to high-throughput screening for illegally added ingredients in cosmetics by high performance liquid chromatography-time-of-flight mass spectrometry (HPLC-Q TOF MS/MS). Methods: Through high-throughput screening of the initial risk assessment of children’s cosmetics sold in markets by HPLC-Q TOF MS/MS, a batch of tacrolimus positive children’s cosmetics was identified, and then a method was established for qualitative and quantitative determination by HPLC-MS/MS. After the optimization of chromatographic analysis conditions, the gradient elution was performed on a Waters ACQUITY UPLC BEH C18 column at 45 ℃, which were used an aqueous solution (containing 17.5 mmol·L-1 acetic acid -5 mmol·L-1 ammonium acetate) and a methanol solution (containing 17.5 mmol·L-1 acetic acid-5 mmol·L-1 ammonium acetate) as mobile phases at the flow rate of 0.3 mL·min-1. The analytes were scanned by HPLC-MS/MS in positive ion multiple reaction monitoring mode. Results: There was a good linear relationship between Tacrolimus and pimecrolimus in the concentration range of 0.5-50 ng·mL-1.The limits of detection were 10 ng·g-1and the limits of quantification concentration were 25 ng·g-1. The spiked recoveries of each concentration level were good, which ranged from 93.1% to 110.7% in the four respective matrices, such as cream, emulsion, water and oil. Tacrolimus was detected in 1 batch of children’s cosmeticsat 2.8 mg·kg-1. Conclusion: This method makes up for the lack of test methods for tacrolimus and pimecrolimus illegally addition in cosmetics, and provides technical supports for the daily supervision in cosmetics.
NIU Shui-jiao, YU Hai-ying, DONG Ya-lei, WANG Hai-yan, LIU Hui-xiang, SUN Lei, LI Qi-yan
. Determination of tacrolimus and pimecrolimus illegally added in cosmetics by HPLC-MS/MS[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(10)
: 1759
-1765
.
DOI: 10.16155/j.0254-1793.2023.10.14
[1] 胡珊. 特应性皮炎诊疗研究的进展[J]. 中国当代医药, 2021, 28(28):25
HU S. Advances in diagnosis and treatment of atopic dermatitis[J]. China Mod Med, 2021, 28(28):25
[2] 曹华. 他克莫司在皮肤科的临床应用[J]. 皮肤科学通报, 2021, 38(4):343
CAO H. Clinical application of tacrolimus in dermatology[J]. Dermatol Bull, 2021, 38(4):343
[3] NGHIEM P, PEARSON G, LANGLEY RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis[J]. J Am Acad Dermatol, 2002, 46(2):228
[4] 国家药典委员会.中华人民共和国药典临床用药须知 化学药和生物制品卷[M]. 北京: 中国医药科技出版社, 2015
State Pharmacopoeia Commission. The Pharmacopoeia of the People’s Republic of Clinical Medication Notice Chemical Drugs and Biological Products Volume[M]. Beijing: China Medical Science Press, 2015
[5] CHIA BK, TEY HL. Systematic review on the efficacy, safety, and cost-effectiveness of topical calcineurin inhibitors in atopic dermatitis[J]. Dermatitis, 2015, 26(3):122
[6] 刘玲玲, 窦侠, 谢志强, 等. 他克莫司软膏治疗儿童特应性皮炎疗效和安全性研究[J]. 中华皮肤科杂志, 2005, 38(10):608
LIU LL, DOU X, XIE ZQ, et al. Efficacy and safety of tacrolimus ointment for the treatment of atopic dermatitis in Chinese children[J]. Chin J Dermatol, 2005, 38(10):608
[7] 汪科, 朱学骏. 局部免疫调节剂他克莫司、吡美莫司在皮肤病的应用[J]. 药物不良反应杂志, 2005, 7(5):345
WANG K, ZHU XJ. Topical immunomodulators tacrolimus and pimecrolimus used for dermatosis[J]. Adv Drug React J, 2005, 7(5):345
[8] 白文永. 他克莫司与吡美莫司治疗特应性皮炎的系统评价[D]. 济南: 山东大学, 2009
BAI WY. Systematic Review of Tacrolimus and Pimecrolimus in The Treatment of Atopic Dermatitis[D]. Jinan: Shandong University, 2009
[9] 蒋冲. 长期外用他克莫司软膏对特应性皮炎患者免疫力的影响[D]. 广州: 南方医科大学, 2013
JIANG C. The Influence of Long-Term Topical Tacrolimus Ointment on Immunity of Patients with Atopic Dermatitis[D]. Guangzhou: Southern Medical University, 2013
[10] 吴景, 邢书霞, 王钢力. 化妆品中非法添加禁用物质检测技术研究进展[J]. 日用化学品科学, 2015, 38(10):5
WU J, XING SX, WANG GL. Research progress on determination technologies for prohibited substances illegally added in cosmetics[J]. Deterg Cosmet, 2015, 38(10):5
[11] 王延东, 唐细兰, 叶成添, 等. 高效液相色谱法测定吡美莫司滴眼液的含量[J]. 中国新药杂志, 2010, 19(21):2005
WANG YD, TANG XL, YE CT, et al. Determination of pimecrolimus in eye drops by HPLC[J]. Chin New Drugs J, 2010, 19(21):2005
[12] 陈悦. HPLC法测定他克莫司的含量及有关物质[J]. 药物分析杂志, 2008, 28(2):309
CHEN Y. HPLC determination of tacrolimus and its related substances[J]. Chin J Pharm Anal, 2008, 28(2):309
[13] 莎日娜, 张冬婕, 赵志刚, 等. UHPLC-MS/MS测定人全血他克莫司浓度的不确定度评定[J]. 中国药师, 2021, 24(9):1752
SHA RN, ZHANG DJ, ZHAO ZG, et al. Uncertainty evaluation for tacrolimus analysis in human whole blood by UHPLC-MS/MS[J]. China Pharm, 2021, 24(9):1752
[14] 夏路风, 薛峰, 刘蕾, 等. HPLC-MS/MS测定肝移植早期患者全血中他克莫司的浓度[J]. 药物分析杂志, 2010, 30(9):1672
XIA LF, XUE F, LIU L, et al. HPLC-MS/MS determination of blood tacrolimus concentrations in early liver transplant recipients[J]. Chin J Pharm Anal, 2010, 30(9):1672
[15] 秦伟, 王晓雪, 张相林, 等. 他克莫司浓度在移植患者全血、血浆与血细胞中的相关性研究[J]. 中国药房, 2019, 30(15):2105
QIN W, WANG XX, ZHANG XL, et al. Correlation of tacrolimus concentrations among transplant patients’ whole blood, plasma and blood cells[J]. China Pharm, 2019, 30(15):2105
[16] MEI S, WANG J, CHEN D, et al. Simultaneous determination of cyclosporine and tacrolimus in human whole blood by ultra-high performance liquid chromatography tandem mass spectrometry and comparison with a chemiluminescence microparticle immunoassay[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1087-1088: 36
