HPLC-MS/MS法同时测定三高(高血糖、高血脂、高血压)人群用保健食品中添加的45个化学药物

目的：建立高效液相色谱串联质谱法（HPLC-MS/MS法）同时测定三高（高血糖、高血脂、高血压）人群用保健食品中45个违法添加的化学药物。方法：采用5 mmol·L^-1乙酸铵溶液（用甲酸调节pH至3.0）和乙腈，在Agilent Eclipse Plus C₁₈柱（100 mm×2.1 mm，1.8 μm）上进行梯度洗脱，流速为0.2 mL·min^-1；质谱采用电喷雾离子源（ESI）正负离子模式将样品离子化，并用多反应监测（MRM）模式对45个化学药物进行测定。结果：45个化学药物在各自考察范围内线性良好，相关系数均大于0.995 0；平均回收率（n=3）为63.3%~129.5%（RSD：0.20%~9.9%），精密度和稳定性试验的RSD分别为0.50%~9.7%，1.0%~9.9%；正离子模式下检测下限为0.02~7 ng·g^-1，负离子模式下检测下限为128 ng·g^-1。300批样品中共检出3批阳性样品，检出物分别是苯乙双胍、格列本脲、氢氯噻嗪和氨氯地平。结论：该HPLC-MS/MS法可用于测定三高人群用保健食品中45个违法添加的化学药物。

Objective: To establish an ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of 45 illegal addition chemical drugs in hyperglycemic, hyperlipidemic and hypertensive people's health foods. Methods: 45 illegal addition components were well separated by the gradient elution of 5 mmol·L^-1 ammonium acetate aqueous solution (adjust to pH 3.0 with formic acid) and acetonitrile on an Agilent Eclipse Plus C₁₈ (100 mm×2.1 mm,1.8 μm) at a flow rate of 0.2 mL·min^-1. MS detection was carried out by positive/negative electrospray ionization (ESI) mass spectrometer in multiple reaction monitor (MRM) mode. Results: The method validation showed good linarites with correlation coefficients (r²) above 0.995 0 for all components. The mean recoveries ranged from 63.3% to 129.5% (RSD:0.20%-9.9%). The RSD values for precision were in the ranges of 0.50% to 9.7%,while those for stability were in the ranges of 1.0% to 9.9%. Meantime,the LOD values in positive mode were in the range of 0.02-7 ng·g^-1,while the LOD was 128 ng·g^-1 in negative mode. 3 batches of positive samples were detected in 300 batches of samples, and the components were phenformin,glibenclamide,hydrochlorothiazide and mlodipine. Conclusion: This HPLCMS/MS method can be used for determination of 45 illegal addition components in hyperglycemic,hyperlipidemic and hypertensive people's health foods.

[1] 董芳,杜怡峰.代谢综合征与老年缺血性脑卒中继发血管性认知功能障碍的相关性分析[J].中国现代医学杂志,2017,27(27):71 DONG F, DU YF. Relationship between metabolic syndrome and vascular cognitive impairment in elderly patients after ischemic stroke[J]. China J Mod Med,2017, 27(27):71
[2] GISELA CM, JOSE PC, LUIZ ASC, et al. Prevalence of metabolic syndrome:association with risk factors and cardiovascular complications in an urban population[J]. PLoS One, 2014, 9(9):1
[3] 杜彦山,李强,吴春敏,等.超高效液相色谱-四极杆/静电场轨道阱高分辨质谱快速筛查及定量分析保健品中11种非法添加降糖药物[J].色谱, 2015, 33(4):371 DU YS, LI Q, WU CM, et al.Rapid screening and quantitative detection of 11 illegally added antidiabetics in health care products by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry[J].Chin J Chromatogr, 2015, 33(4):371
[4] 朱青霞,曹永兵,曹颖瑛,等. TLC-SERS法快速检测降压类中药中非法添加的四种化学成分[J].光谱学与光谱分析,2014, 34(4):990 ZHU QX, CAO YB, CAO YY, et al.Rapid detection of four antipertensive chemicals adulterated in traditional Chinese medicine for hypertension using TLC-SERS[J].Spectrosc Spect Anal,2014, 34(4):990
[5] 陈玉武,张夙萍,高晓昱. 薄层色谱法初筛少数中药制剂中添加降糖类化学药物[J]. 药物分析杂志, 2010, 30(7):1298 CHEN YW, ZHANG SP, GAO XY. TLC initial screening of a few of tradition Chinese medicine preparation added hypoglycemic of chemical drug[J].Chin J Pharm Anal, 2010, 30(7):1298
[6] 王铁松,仝禹,郑洁,等.薄层色谱法快速筛查降脂、降压、止咳平喘类中药制剂中的29种添加化学药品[J].中国药学杂志, 2010, 45(11):857 WANG TS,TONG Y,ZHENG J,et al. Detection of 29 adulterations in lipid-regulating, antihypertensive, antitussive and antiasthmatic herbal remedies by TLC[J]. Chin Pharm J, 2010, 45(11):857
[7] 王豆,杨欣,程怡凡,等. 高效液相色谱法同时鉴定保健胶囊食品中非法添加的9种降糖药成分[J]. 药物分析杂志,2013, 33(8):1377 WANG D, YANG X, CHENG YF, et al. Identification of nine components of antidiabetic medicine to health food capsules by HPLC[J]. Chin J Pharm Anal,2013, 33(8):1377
[8] 余小平,郑明,陈蕾.降糖保健食品和中成药中12种化学药的液相快速筛查[J]. 中国现代应用药学, 2013, 30(8):882 YU XP, ZHENG M, CHEN L. Rapid screening of 12 anti-diabetic agents in traditional Chinese medicines and health care products by HPLC[J]. Chin J Mod App Pharm,2013, 30(8):882
[9] 隋海山,王立娟,谢菲. 高效液相色谱-二极管阵列检测器法测定保健食品和中成药中违法添加的10种降糖类西药[J].中国药业, 2015, 24(22):110 SUI HS, WANG LJ, XIE F. Detection of 10 kinds of antidiabetics illegally added in traditional Chinese medicines and health care products by HPLC-DAD[J]. China Pharm, 2015, 24(22):110
[10] 王琤帅,舒展,朱洁,等. 中成药和保健食品中18种非法添加降压药物的HPLC-QTOF/MS定性检测[J]. 中国药师,2016, 19(6):108 WANG ZS, SHU Z, ZHU J, et al. Detection of 18 antihypertensive agents illegally added in traditional Chinese medicines and healthy care products by HPLC-QTOF/MS[J]. China Pharm, 2016, 19(6):1084
[11] 姜树银,郭常川,石峰,等.Q-Orbitrap高分辨质谱用于降血脂类中成药和保健食品中非法添加物的快速筛查、鉴定和定量[J]. 药物分析杂志, 2015, 35(8):1447 JIANG SY, GUO CC, SHI F, et al. Application of Q-Orbitrap high resolution mass spectrometry to the detection of illegal adulterated antihyperlipidemics in herbal medicines and dietary supplements[J]. Chin J Pharm Anal,2015, 35(8):1447
[12] GUO CC, SHI F, JIANG SY, et al.Simultaneous identification, confirmation and quantitation of illegal adulterated antidiabetics in herbal medicines and dietary supplements using high-resolution benchtop quadrupole-Orbitrap mass spectrometry[J]. J Chromatogr B, 2014, 967:174
[13] 丁博,王志元,谢建军,等. QuEChERS前处理技术联合液相色谱-四极杆飞行时间质谱法检测保健食品中24种违禁降血糖、降血压和降血脂药物[J].色谱, 2016, 34(6):583 DING B, WANG ZY, XIE JJ, et al. Determination of 24 antihyperglycemic, antihypertensive and antihyperlipidemic drugs illegally added in health food samples by liquid chromatographyquadrupole-time of flight mass spectrometry[J]. Chin J Chromatogr,2016, 34(6):583
[14] 马萍,李鹏飞,刘丽宏,等. HPLC-MS/MS法同时测定人血浆中替米沙坦和氢氯噻嗪的浓度[J].质谱学报,2011, 32(1):43 MA P, LI PF, LIU LH, et al.Determination of telmisartan and hydrochlorothiazide in human plasma by HPLC-MS/MS[J]. J Chin Mass Spectrom Soc,2011, 32(1):43
[15] 王杨,高丽英,吴艳平,等. 6种他汀类药物的电喷雾离子阱质谱分析[J].质谱学报,2010, 31(6):368 WANG Y, GAO LY, WU YP, et al. Analysis of six statins by electrospray ion trap mass spectrometry[J]. J Chin Mass Specrom Soc,2010, 31(6):368