目的:建立了市售抗鼻炎凝胶类产品中激素非法添加检测方法,对采集的来源于网络销售的22批次产品进行检测,并对暴露风险进行评估,提出监管建议。方法:试样中40个激素类非法添加物采用乙腈提取,高效液相色谱分离,串联质谱检测,基质外标法定量,考察测定方法学,对市售样品进行检测。结果:方法学考察试验表明,40个激素类非法添加物线性关系良好,方法精密度、重复性、回收率符合方法学要求。对市售的22批样品进行检测,总体检出阳性率为45.5%(10/22),其中械字号产品检测7批次,非法添加物检出阳性2批次,涉及非法添加倍氯米松双丙酸酯(1批次)和氯倍他索丙酸酯(1批次);消字号产品检测15批次,检出阳性8批次,涉及非法添加氯倍他索丙酸酯(7批次)和布地奈德(1批次)。结论:监测结果显示,网络销售的械字号和消字号鼻炎治疗及相关产品存在系统性的激素非法添加问题,可能产生系统性的特定人群暴露风险,亟需对网络销售的械字号和消字号鼻炎治疗及相关产品加强监管、整顿。在监测过程中检出3种激素类药物,建议加强对激素类原料药的监管。
Objective: To establish a method for detecting illegal addition of hormone in anti rhinitis gel products. Twenty-two products from online sales were tested. Exposure risks and regulatory suggestions were proposed from the monitoring results. Methods: Forty Illegal hormone additives in the sample were extracted with acetonitrile, separated by high performance liquid chromatography, detected by tandem mass spectrometry and quantified by matrix external standard method. The test methodology was evaluated and samples were determined. Results: The method showed a good linear relationship with 40 illegal hormone additives, and met the methodological requirements of precision, repeatability and recovery. Twenty-two samples were tested, and the total positive rate was 45.5% (10/22). Two in seven of medical device samples were tested positive, involving the illegal addition of beclomethasone dipropionate and clobetasopronate. Eight in fifteen hygienic samples were tested positive, including the illegal addition of clobetasopronate and budesonide. Conclusion: According to the monitoring results, there might be a systematic exposure of illegal hormone addition within the related online products, and may cause the systematic risks. It is necessary to strengthen the supervision and rectification of the rhinitis treatment and related products sold online. Meanwhile, since three kinds of hormone drugs were detected, supervision of hormone APIs should also be strengthened.
[1] RHEN T, CIDLOWSKI JA. Anti-inflammatory action of glucocorticoids-new mechanisms for old drugs [J]. N Engl J Med, 2005, 353 (16):1711
[2] SCHACKE H, DOCKE WD, ASADULLAH K. Mechanisms involved in the side effects of glucocorticoids [J]. Pharmacol Ther, 2002, 6(1):23
[3] 陈桂琴, 肖树雄, 黄佳颖, 等. 化妆品非法添加特点及检测研究 [J]. 中国食品药品监管, 2022 (10):72
CHEN GQ, XIAO SX, HUANG JY, et al. Study on the characteristics and detection of illegal addition of cosmetics [J]. China Food Drug Admin Mag, 2022(10):72
[4] 李帅, 周宏斌, 翁东海, 等. 240件婴幼儿护理产品中41种糖皮质激素的检测结果 [J]. 香料香精化妆品, 2022 (2):41
LI S, ZHOU HB, WONG DH, et al. Detection results of 41 glucocorticoids in 240 infant care products [J]. Flav Fragr Cosm, 2022 (2):41
[5] 肖树雄, 黄佳颖, 周志明, 等. 化妆品非法添加成分检测流程优化研究 [J]. 中国食品药品监管, 2022, 5:60
XIAO SX, HUANG JY, ZHOU ZM, et al. Research on optimizing screening process for illegal additions in cosmetics [J]. China Food Drug Admin J, 2022, 5:60
[6] VAN HEUGTEN AJP, DE BOER W, DE VRIES WS, et al. Development and validation of a stability-indicating HPLC-UV method for the determination of triamcinolone acetonide and its degradation products in an ointment formulation [J]. J Pharm Biomed Anal, 2018, 149: 265
[7] 王欣然, 董亚蕾, 王海燕, 等. 化妆品中激素类成分检验的研究与进展 [J]. 中国食品药品监管, 2021, 8:52
WANG XR, DONG YL, WANG HY, et al. Reasearch and development of hormone detection in cosmetics [J]. China Food Drug Admin J, 2021, 8:52
[8] 孙夏荣, 史达, 曹玉, 等. 超高效液相色谱-串联质谱法同时测定外用贴膏剂中非法添加 48个化合物 [J]. 药物分析杂志, 2020, 40(3):502
SUN XR, SHI D, CAO Y, et al. Simultaneous determination of 48 compounds illegally added in emplastrum by UPLC-MS/MS [J]. Chin J Pharm Anal, 2020, 40(3):502
[9] SCIPPO ML, DEGAND G, BROSE F, et al. Control of the illegal administration of natural steroid hormones in urine and tissues of veal calves and in plasma of bulls [J]. Anal Chim Acta, 1993, 275(1-2):57
[10] MANOJ KN, POONAM K, MANOJ KP, et al. Functional nanomaterials based opto-electrochemical sensors for the detection of gonadal steroid hormones [J]. TrAC Trends Anal Chem, 2022, 150: 116571
[11] 国家市场监督管理总局. 食品补充检验方法 饮料、茶叶及相关制品中对乙酰氨基酚等59种化合物的测定 [S]. 2017
State Administration for Market Regulation. BJS 201713 Determination of 59 Compounds such as Acetaminophen in Beverages,Tea and Related Products [S]. 2017
[12] 国家药品监督管理局2019年第66号通告[B]. 化妆品中激素类成分的检测方法
Notification No. 66 of the NMPA (2019)[B]. Detection of Hormone Components in cosmetics
[13] 张虹艳, 邱国玉, 石晓峰, 等. 高效液相色谱-四极杆-飞行时间质谱法快速筛查保健食品中10种雄性激素类非法添加物 [J]. 分析测试学报, 2020, 39(9):1085
ZHANG HY, QIU GY, SHI XF, et al. Rapid screening of 10 illegally adulterated androgen drugs in health foods by high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry [J]. J Instrum Anal, 2020, 39(9):1085
[14] LI QY, LI GL, FAN LH, et al. Click reaction triggered turn-on fluorescence strategy for highly sensitive and selective determination of steroid hormones in food samples [J]. Food Chem, 2022, 174:131565
[15] VAN NL, QUANG TN, NGOC TN, et al. Simultaneous determination of plant endogenous hormones in green mustard by liquid chromatography-tandem mass spectrometry [J]. Chin J Anal Chem, 2021, 49(12):111
[16] SAMIA M, FADL M, ENGIE EL, et al. Development of a new liquid chromatography-tandem mass spectrometry method for the determination of hormones in bovine muscle [J]. J Pharm Biomed Anal, 2020, 190: 113550
[17] WANG SC, QI PP, DI SS, et al. Significant role of supercritical fluid chromatography-mass spectrometry in improving the matrix effect and analytical efficiency during multi-pesticides residue analysis of complex chrysanthemum samples [J]. Anal Chim Acta, 2019, 1074:108
[18] BEHNAM K, JIANG XY, PEGGY H, et al. Matrix effect on food allergen detection: A case study of fish parvalbumin [J]. Food Chem, 2019, 274:526
[19] VICKI. B (Edit), Eurachem/CITAC Guide: Guide to Quality in Analytical Chemistry: An Aid to Accreditation (3rd ed. 2016). ISBN 978-0-948926-32-7. Available from www.eurachem. org[EB/OL]. [2022-07-08]. https://www.eurachem.org/images/stories/Guides/pdf/Eurachem_CITAC_QAC_2016_EN. pdf
[20] ICH Expert Working Group.Validation of analytical procedures: test and methodology Q2 (R1). Ich Harmonised Tripartite Guideline[EB/OL]. [2022-07-08]. https://database.ich.org/sites/default/files/Q2_R1_Guideline.pdf
[21] QIAO D, LIU HH, ZHANG XM, et al. Exploring the potential of thyroid hormones to predict clinical improvements in depressive patients: a machine learning analysis of the real-world based study [J]. Affec Disorders, 2022, 299:159
[22] MAJID R, ZOHREH SH. The effect of synbiotic supplementation on thyroid hormones, blood pressure, depression and quality of life in hypothyroid patients: a study protocol for a randomized double-blind placebo controlled clinical trial [J]. Clin Nutr ESPEN, 2022, 48:472
[23 ] SEAN S (Edit). Martindale: The complete Drug Reference 36th Edition [M]. London: Pharmaceutical Press, 2009:168
[24] YAEL B, KFIR B, ITAY I, et al. The impact of tumor detection method on genomic and clinical risk and chemotherapy recommendation in early hormone receptor positive breast cancer [J]. Ther Breast, 2021, 60:78
[25] KATHRYN G, JORDYN C, JULIANA C, et al. Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats [J]. Drug Alcohol Depend, 2017, 174:137
[26] UNTERSMAYR E, JENSEN AN, WALCH K. Sex hormone allergy: clinical aspects, causes and therapeutic strategie-update and secondary publication [J]. World Aller Organ J, 2017, 10:45
