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

目的：建立一种快速、准确检测常见的贴膏制剂中非法添加48个糖皮质激素类、非甾体抗炎类等化合物方法。方法：采用超高效液相色谱-串联质谱法，Agilent EclipsePlus C₁₈ RRHD色谱柱（50 mm× 3.0 mm，1.8 μm）分离，以10 mmoL·L^-1乙酸铵溶液（含0.1%甲酸）作为流动相A，以乙腈作为流动相B，梯度洗脱；电喷雾电离（ESI），正负离子扫描，动态多反应监测（DMRM）模式采集数据。结果：48个非法添加的化合物在相应的测定范围内线性关系良好，相关系数均大于0.99，在3个不同浓度加标水平下，平均回收率为70.3%~118.5%，RSD为3.8%~10.9%，各化学药物的检测下限在0.02~1.25 mg·kg^-1，收集的20批次样品中，1批次检出氢化可的松和地塞米松，含量分别为1.5、0.8 mg·g^-1，1批次检出双氯芬酸钠，含量为1.2 mg·g^-1。结论：该方法操作简便，准确、快速，灵敏度高，适用于贴膏制剂中非法添加48个化合物的定性筛查和定量检测。

Objective: To establish a rapid and accurate method for simultaneous detection of 48 glucocorticoids and non-steroidal anti-inflammation compounds which were illegally added into the emplastrum.Methods: The compounds in samples were separated on an Agilent Eclipse Plus C₁₈ RRHD column(50 mm×3.0 mm, 1.8 μm).The mobile phase was composed of 10 mmoL·L^-1 ammonium acetate solution(containing 0.1% formic acid) (A)and acetonitrile(B)with gradient elution.Dynamic multi-reaction monitoring(DMRM)scanning was employed for quantification with switching electrospray ion source polarity in positive and negative ions.Results: Forty-eight compounds which were illegally added showed good linear relationships within their own ranges,the correlation coefficients(r)were above 0.99.Under three different concentration levels,their average recoveries ranged from 70.3% to 118.5% with the RSDs of 3.8% to 10.9%.The LODs were all in range of 0.02-1.25 mg·kg^-1.Among the 20 batches of samples collected,hydrocortisone and dexamethasone were detected in one batch,with the content of 1.5 mg·g^-1 and 0.8 mg·g^-1,respectively,and diclofenac sodium was detected in one batch,with the content of 1.2 mg·g^-1.Conclusion: The method is simple,accurate,rapid,and highly sensitive,and can be used for the qualitative screening and quantitative determination of illegally added 48 components in Emplastrum.

[1] 鲁艺,韩东岐,黎雪清,等.安神类和抗风湿类中药和保健食品中非法添加化学成分的案例分析[J].中国药事,2015,29(8):775 LU Y,HAN DQ,LI XQ,et al.Case analysis of sedative-hypnotic and anti-rheumatic chemicals added illegally in herb preparations and health foods[J].Chin Pharm Aff,2015,29(8):775
[2] 马萍,李鹏飞.LC-MS/MS高通量快速筛查中成药和保健品中未知非法添加药物[J].中国药物警戒,2013,10(1):19 MA P,LI PF.High throughput and rapid screening for illegally added chemicals in Chinese patent medicines and health products by LC-MS/MS[J].Chin J Pharmacovigil,2013,10(1):19
[3] 周建良,方翠芬,陈勇,等.快速液相色谱-串联质谱联用同时检测抗风湿类中成制剂中13种添加化学药物成分[J].药物分析杂志,2013,33(2):281 ZHOU JL,FANG CF,CHEN Y,et al.Simultaneous determination of 13 chemicals added in anti-rheumatic traditional Chinese medicines by rapid resolution liquid chromatography coupled with tandem mass spectrometry[J].Chin J Pharm Anal,2013,33(2):281
[4] 黎雪清,谭渺,蒋创杰,等.HPLC法快速筛查抗风湿类中成药和保健食品中24种非法添加化学成分[J].中成药,2014,36(9):1891 LI XQ,TAN M,JIANG CJ,et al.Rapid screening of 24 chemicals added illegally in anti-rheumatic herb preparations and health foods by HPLC[J].Chin Tradit Pat Med,2014,36(9):1891
[5] 张鹤,黄子桐,朱禹彭,等.关于抗风湿类中药制剂中非法添加化学药品的检测方法研究[J].亚太传统医药,2010,6(6):31 ZHANG H,HANG ZT,ZHU YP,et al.Preparation of anti-rheumatic medicine illegally added chemical detection method[J].Asia Pac Tradit Pat Med,2010,6(6):31
[6] 张学斌,施介华.HPLC鉴定抗风湿中药制剂中非法添加的6种西药成分[J].中国现代应用药学,2010,27(2):160 ZHANG XB,SHI JH.Determination of pharmaceutical component in the traditional chinese antirheumatic by RP-HPLC-DAD[J].Chin J Mod Appl Pharm,2010,27(2):160
[7] 顾炳仁,许奇,缪刚.UPLC同时测定中成药及保健品中非法添加12种激素成分[J].药物分析杂志,2010,30(11):2185 GU BR,XU Q,MIU G.UPLC determination of 12 hormones illegally adulterated into traditional Chinese medicines and health product[J].Chin J Pharm Anal,2010,30(11):2185
[8] 田兰,张继春,陈睿,等.超高效液相色谱-串联四极杆质谱法检测镇静安神类中药制剂及保健品中非法添加的9种化学药品[J].中国药业,2013,22(6):66 TIAN L,ZHANG JC,CHEN R,et al.Detection of 9 kinds of illegally added chemical medicines in traditional Chinese medicine phenobarb ital preparations and health foods by UPLC-MS/MS[J].China Pharm,2013,22(6):66
[9] 李欣荣,陈安珍,杨钊.UPLC-MS/MS检测消肿止痛类中成药中违禁添加的双氯芬酸钠和氨基比林[J].药物分析杂志,2010,30(7):1294 LI XR,CHEN AL,YANG Z.UPLC-MS/MS detection of diclofenac sodium and aminophenazone in traditional Chinese medicines preparation of detumescent analgesic category[J].Chin J Pharm Anal,2010,30(7):1294
[10] 刘志辉.HPLC法同时测定抗风湿类中成药及保健品中非法添加9种解热镇痛类化学药物[J].中国药师,2015,18(7):1116 LIU ZH.Simultaneous determination of nine antipyretic analgesic drugs illegally added into anti-rheumatic traditional Chinese medicines and health products by HPLC[J].ChinA Pharm,2015,18(7):1116
[11] 李克庆,许啸,庄晓庆,等.HPLC法测定天麻胶囊中非法添加的醋酸泼尼松[J].药物分析杂志,2007,27(8):1246 LI KQ,XU Q,ZHUANG XQ,et al.HPLC determination of prednisone acetate added illegally in Tianma capsules[J].Chin J Pharm Anal,2007,27(8):1246
[12] 黄卫平,李琴,唐靓,等.超高效液相色谱-四极杆飞行时间质谱测定抗风湿类中药非法添加的化学药物成分[J].中华中医药学刊,2014,32(11):2707 HUANG WP,LI Q,TANG L,et al.Determination of chemical components illegally mixed in antirheumatic traditional Chinese medicine by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry[J].Chin Arch Tradit Chin Med,2014,32(11):2707
[13] 王戈,赵培敬.高效液相色谱-质谱联用法检查止喘灵胶囊中非法添加的醋酸泼尼松和茶碱[J].中国药业,2013,22(4):40 WANG G,ZHAO PJ.Determination of prednisone acetate and theophylline illegally added into Zhichuanling capsules by HPLC-MS/MS[J].China Pharm,2013,22(4):40
[14] 刘放,唐靓.抗风湿中药制剂中非法添加多种化学成分的HPLC检测[J].西北药学杂志,2014,29(1):18 LIU F,TANG L.Determination of the illegal addictives in the traditional Chinese antirheumatic preparations by RP-HPLC-UV[J].Northwest Pharm J,2014,29(1):18
[15] 钱叶飞,贾昌平,鲁辉,等.UPLC-MS-MS快速检测中成药及保健食品中非法添加的38种糖皮质激素[J].中国实验方剂学杂志,2016,22(10):60 QIAN YF,JIA CP,LU H,et al.Rapid determination of 38 glucocorticoids illegally added into Chinese patent medicines and dietary supplements by UPLC-MS-MS[J].Chin J Exp Tradit Med Form,2016,22(10):60
[16] 石善玉.糖皮质激素结合特布他林治疗慢阻肺急性加重期的疗效及不良反应观察[J].中国现代药物应用,2018,12(24):77 SHI SY.Observation on efficacy and adverse reactions of glucocorticoid combined with terbutaline in the trea tment of acute exacerbation of chronic obstructive pulmonary disease[J].Chin J Mod Appl Pharm,2018,12(24):77