环境中药物与个人护理品监测技术参考课件.ppt

1、环境中药物与个人护理品监测技术环境中药物与个人护理品监测技术邵兵北京市疾病预防控制中心1 PPCPsPPCPs定义定义:Environ.Health.Perspect,1999,107 处方药处方药 非处方药非处方药 如抗生素、类固醇、止痛如抗生素、类固醇、止痛药、降压药、避孕药、催眠药和药、降压药、避孕药、催眠药和减肥药等减肥药等 肥皂、香波、牙膏、香肥皂、香波、牙膏、香水、护肤品、防晒霜、发胶、水、护肤品、防晒霜、发胶、染发剂等染发剂等 2环境中环境中PPCP排放排放http:/www.york.ac.uk/depts/eeem/gsp/esm/issues/pharma.htm制药厂污水

2、处理环境水体土壤粪污贮存农田施放畜产养殖水产养殖宠物饲养人体医疗药物及容器不恰当处置3研究背景研究背景 PPCPs无处不在无处不在 Ubiquitous持久性持久性 Persistence毒性（耐药性等）毒性（耐药性等）ToxicityPossible risks of PPCPs4抗生素耐药性抗生素耐药性细菌耐药性细菌耐药性 存在形式存在形式金葡菌对青霉素金葡菌对青霉素G G的耐药率的耐药率已达已达90%90%2006200620072007年度大肠杆菌年度大肠杆菌对合成喹诺酮类抗菌药物耐对合成喹诺酮类抗菌药物耐药性高达药性高达70%70%，给临床治疗，给临床治疗带来新的困难带来新的困难 耐

3、药菌在人和动物体内发现耐药菌在人和动物体内发现 一些抗药菌或者抗多种抗生一些抗药菌或者抗多种抗生素的病原菌不但存在于畜禽素的病原菌不但存在于畜禽养殖场与城市污水厂、部分养殖场与城市污水厂、部分土壤和沉积物中，也存在于土壤和沉积物中，也存在于一些比较干净的湖泊和饮用一些比较干净的湖泊和饮用水中水中 5 超高效液相色谱-串联质谱法 测定屠宰废水中78种兽药 6 2004年我国生猪出栏约年我国生猪出栏约4.8亿头，亿头，2006年达到年达到6.3亿头，到亿头，到2010年将达到年将达到7.3亿头，生猪资源非常丰富。预计亿头，生猪资源非常丰富。预计“十十一五一五”期间我国肉类年均增长期间我国肉类年均增

4、长35。2005年，年，90,000吨抗生素被用于动物饲吨抗生素被用于动物饲养。养。中国生猪出栏量7预防和治疗动物传染病预防和治疗动物传染病削弱胃肠内有害微生物，抑制、杀死致病菌，增强抗削弱胃肠内有害微生物，抑制、杀死致病菌，增强抗病能力，以防禽畜病瘟病能力，以防禽畜病瘟促进生长促进生长使动物肠壁变薄，有利于养分的渗透和吸收，提高饲使动物肠壁变薄，有利于养分的渗透和吸收，提高饲料利用率料利用率刺激动物脑下垂体分泌激素，促进机体生长发育（增刺激动物脑下垂体分泌激素，促进机体生长发育（增重重10-20%）畜禽养殖中兽药的作用（10%）（90%）8 屠 宰 场 流 程 图978 种种 检检 测测 对

5、对 象象13种种-受体激动剂受体激动剂10种种-受体阻断剂受体阻断剂6种利尿剂种利尿剂7种镇静剂种镇静剂10 色谱柱：Waters Acquity BEH C18柱，100mm2.1 mm(id)，粒径1.7 um。进样室温度：5；进样体积：10 uL。流动相：ESI+模式，A为0.1%甲酸水，B为甲醇 ESI-模式，A为纯水，B为乙腈 流速：0.3 ml/min。色谱条件色谱条件11离子源模式ESI ESI 毛细管电压3.0 kV2.8 kV脱溶剂气流量500 L h-1源温度100C脱溶剂温度350C倍增电压650V碰撞室压力3.2 103 mbar质谱条件质谱条件12stdTime2.0

6、04.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-31:MRM of 2 Channels ES+173 1562.85e61.4020080902-32:MRM of 6 Channels ES+273

7、 2556.69e72.5020080902-32:MRM of 6 Channels ES+240.2 147.84.09e72.8320080902-32:MRM of 6 Channels ES+226 151.72.90e72.6720080902-33:MRM of 10 Channels ES+279.1 124.17.74e63.0520080902-33:MRM of 10 Channels ES+279 124.18.63e63.0520080902-33:MRM of 10 Channels ES+267.1 189.72.60e72.88stdTime2.004.006.

8、008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-36:MRM of 8 Channels ES+370.2 325.99.34e64.5120080902-36:MRM of 8 Channels ES+281 155.98.89e64.4620080902-36:MRM of 8 Channels ES+271 155.92.12e74.5720080902-36:MRM of 8 Channel

9、s ES+268 155.97.13e64.51stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-37:MRM of 6 Channels ES+362.1 318.13.87e74.7220080902-37:MRM of 6 Channels ES+334.1 316.13.76e64.7420080902-37:MRM of 6 Channels ES+321.

10、1 3034.26e64.764.514.8620080902-38:MRM of 6 Channels ES+281 1567.45e64.84磺胺索他洛尔沙丁胺醇特布它林磺胺二甲基异嘧啶磺胺二甲基嘧啶阿替洛尔氧氟沙星培氟沙星依诺沙星磺胺甲氧嗪氟罗沙星磺胺5-甲氧嘧啶磺胺甲基硫二嗪磺胺二甲唑标准标准LC-MS/MS色谱图色谱图13stdTime4.006.008.0010.0012.00%01004.006.008.0010.0012.00%01004.006.008.0010.0012.00%01004.006.008.0010.0012.00%01004.006.008.0010.001

11、2.00%01004.006.008.0010.0012.00%01004.006.008.0010.0012.00%010020080902-33:MRM of 10 Channels ES+234.2 1606.84e73.3720080902-33:MRM of 10 Channels ES+229.9 170.67.91e63.2320080902-34:MRM of 4 Channels ES+304.3 134.71.05e73.6020080902-34:MRM of 4 Channels ES+265.1 1563.56e63.8620080902-35:MRM of 6 Ch

12、annels ES+363 72.25.66e64.4020080902-35:MRM of 6 Channels ES+319 300.92.63e74.4320080902-35:MRM of 6 Channels ES+304.1 285.83.30e64.17西马特罗阿米洛地非诺特罗磺胺甲基嘧啶麻保沙星clencyclohexerol吡啶酸stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.0

13、0%01002.004.006.008.0010.0012.00%010020080902-38:MRM of 6 Channels ES+320.1 302.13.24e64.8620080902-38:MRM of 6 Channels ES+263 2456.14e74.8720080902-39:MRM of 6 Channels ES+458.2 4417.81e64.9720080902-39:MRM of 6 Channels ES+445.1 4107.57e74.9720080902-39:MRM of 6 Channels ES+332.2 314.11.49e75.00诺

14、氟沙星克伦丙罗二甲胺四环素四环素环丙沙星标准标准LC-MS/MS色谱图色谱图14标准标准LC-MS/MS色谱图色谱图stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-315:MRM o

15、f 8 Channels ES+380.2 2515.29e77.4420080902-313:MRM of 6 Channels ES+228.1 153.85.13e76.4720080902-313:MRM of 6 Channels ES+268 1164.54e66.0620080902-313:MRM of 6 Channels ES+393.1 349.11.07e76.3820080902-314:MRM of 8 Channels ES+262.9 2452.92e56.8520080902-314:MRM of 8 Channels ES+311.3 236.92.71e7

16、6.8220080902-314:MRM of 8 Channels ES+479.2 4442.38e66.85塞利洛尔妥布特罗美托洛尔司帕沙星西诺沙星马布特罗金霉素stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012

17、.00%010020080902-311:MRM of 8 Channels ES+400.2 382.13.86e65.3620080902-311:MRM of 8 Channels ES+396.4 3522.61e65.3220080902-311:MRM of 8 Channels ES+352 2651.32e75.2220080902-311:MRM of 8 Channels ES+254.2 237.19.99e65.2620080902-312:MRM of 8 Channels ES+465.1 447.97.20e65.6520080902-312:MRM of 8 C

18、hannels ES+386 3423.14e65.5820080902-312:MRM of 8 Channels ES+277.3 202.93.23e75.65二氟沙星洛美沙星氨苯喋啶去甲基金霉素沙拉沙星克伦特罗奥比沙星15stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012

19、.00%010020080902-315:MRM of 8 Channels ES+311 155.91.18e77.3920080902-315:MRM of 8 Channels ES+299.2 115.89.72e67.1220080902-315:MRM of 8 Channels ES+291 202.93.16e77.0420080902-316:MRM of 6 Channels ES+301.2 1561.13e67.9820080902-316:MRM of 6 Channels ES+266.3 115.82.49e67.8720080902-316:MRM of 6 C

20、hannels ES+262 2441.94e67.78stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-317:MRM of 6 Channels ES+443.1 426.11.87e78.498.8920080902-317:MRM of

21、6 Channels ES+325.4 236.91.12e78.7720080902-317:MRM of 6 Channels ES+291 2731.86e58.3720080902-318:MRM of 4 Channels ES+326 115.71.26e79.1320080902-318:MRM of 4 Channels ES+380.1 193.72.19e78.9520080902-319:MRM of 6 Channels ES+260.2 115.84.54e69.93磺胺二甲氧嗪卡拉洛尔克伦潘特磺胺喹啉氧烯洛尔奥索利酸甲稀土霉素马鹏特罗马喷特罗比索洛尔氟哌啶普萘洛尔标

22、准标准LC-MS/MS色谱图色谱图16stdTime2.004.006.008.0010.00%01002.004.006.008.0010.00%01002.004.006.008.0010.00%01002.004.006.008.0010.00%01002.004.006.008.0010.00%01002.004.006.008.0010.00%01002.004.006.008.0010.00%010020080902-319:MRM of 6 Channels ES+233.1 215.13.21e610.3620080902-319:MRM of 6 Channels ES+25

23、0.1 115.87.99e610.2520080902-320:MRM of 8 Channels ES+869.7 696.31.24e710.5310.4120080902-320:MRM of 8 Channels ES+376 164.89.43e710.7720080902-320:MRM of 8 Channels ES+308.2 116.21.41e710.4320080902-320:MRM of 8 Channels ES+262 243.87.69e610.7720080902-321:MRM of 4 Channels ES+327 86.37.98e7萘烯丙洛尔替米

24、考星氟哌啶醇倍它洛尔氟甲奎乙酰丙嗪标准标准LC-MS/MS色谱图色谱图stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-321:MRM of 4 Channels ES+282 236

25、4.16e611.2120080902-322:MRM of 8 Channels ES+916.7 772.44.91e611.6720080902-322:MRM of 8 Channels ES+734.6 158.17.69e511.7120080902-322:MRM of 8 Channels ES+804.6 1746.59e611.6720080902-322:MRM of 8 Channels ES+294.9 266.91.13e711.7520080902-323:MRM of 8 Channels ES+286.9 240.91.54e720080902-323:MRM

26、 of 8 Channels ES+284.9 192.77.04e6硝西泮泰乐菌素红霉素吉他霉素艾司唑仑奥沙西泮安定17stdTime2.002.202.402.602.803.00%01002.002.202.402.602.803.00%01002.002.202.402.602.803.00%0100A-20080902-03:MRM of 6 Channels ES-321.1 152.12.11e62.83A-20080902-03:MRM of 6 Channels ES-357.8 321.86.59e62.982.82A-20080902-03:MRM of 6 Channe

27、ls ES-377.9 305.91.45e62.91stdTime2.004.006.008.0010.0012.00%010020080902-323:MRM of 8 Channels ES+814.6 174.15.64e711.93stdTime2.002.202.402.602.803.00%01002.002.202.402.602.803.00%0100A-20080902-01:MRM of 4 Channels ES-296 2698.19e52.00A-20080902-02:MRM of 4 Channels ES-330 3033.31e62.38麦迪霉素氢氯噻嗪氢氟

28、噻嗪氯霉素甲氯噻嗪三氯噻嗪stdTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-310:MRM of 10 Channels ES+461.2 4263.81e75.0820080902-310:MRM of 10 Channels ES+360 3165.86e65.1020080902-310:MRM of

29、 10 Channels ES+358.1 340.15.94e65.1020080902-310:MRM of 10 Channels ES+302 1646.26e75.0620080902-310:MRM of 10 Channels ES+285.1 155.97.03e65.08土霉素恩诺沙星单诺沙星莱克多巴胺磺胺氯哒酮标准标准LC-MS/MS色谱图色谱图18屠宰场样品屠宰场样品LC-MS/MS色谱图色谱图zhong in blankTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.

30、008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-79:MRM of 6 Channels ES+332.2 314.12.65e64.9720080902-710:MRM of 10 Channels ES+461.2 4265.21e75.0320080902-710:MRM of 10 Channels ES+360 3165.10e65.0620080902-722:MRM of 8 Chan

31、nels ES+916.7 772.41.21e611.6420080902-722:MRM of 8 Channels ES+804.6 1741.85e611.6411.8420080902-723:MRM of 8 Channels ES+284.9 192.74.05e412.08安定吉他霉素泰乐菌素恩诺沙星土霉素环丙沙星zhong in blankTime2.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012

32、.00%01002.004.006.008.0010.0012.00%01002.004.006.008.0010.0012.00%010020080902-7 Sm(Mn,2x3)1:MRM of 2 Channels ES+173 1563.62e41.3620080902-76:MRM of 8 Channels ES+281 155.91.96e64.4420080902-77:MRM of 6 Channels ES+362.1 318.18.91e64.6920080902-77:MRM of 6 Channels ES+334.1 316.15.42e54.704.8220080

33、902-78:MRM of 6 Channels ES+320.1 302.18.54e54.825.0020080902-79:MRM of 6 Channels ES+445.1 4102.16e74.93培氟沙星诺氟沙星四环素氧氟沙星磺胺5甲氧嘧啶磺胺19固体萃取柱的选择固体萃取柱的选择20 Na2EDTA加入量的优化加入量的优化 Na2EDTA的加入对四环素类的回收率的加入对四环素类的回收率影响较大，对其他类物质无影响，影响较大，对其他类物质无影响，500ml水加入水加入1g Na2EDTA就能达到比较好的回就能达到比较好的回收率。收率。21 通过自来水加标实验（每个样品富集通过自来水

34、加标实验（每个样品富集500ml自来水并加入自来水并加入1g Na2EDTA，然后分别调节然后分别调节pH3、5、7、9)。pH=7时大部分物质的回收率时大部分物质的回收率较好。较好。样品样品pH值的优化值的优化结论：结论：22洗脱液洗脱液7.氨基柱洗脱条件的优化氨基柱洗脱条件的优化I.5ml 甲醇甲醇:丙酮丙酮:甲酸甲酸(v:v:v,500:500:1)II.6ml 丙酮丙酮:甲酸甲酸(v:v,1000:1)23 样品前处理样品前处理 500ml500ml水样水样 过滤过滤1gNa1gNa2 2EDTAEDTA振摇、混匀振摇、混匀活化的氨基柱活化的氨基柱（6cc/500mg)抽抽 干干6ml

35、6ml甲醇洗脱甲醇洗脱 5ml(5ml(丙酮丙酮:甲醇甲醇:甲甲酸酸500500:500500:1)1)收集洗脱液收集洗脱液 活化的活化的HLBHLB小小柱柱（6cc/500mg)6cc/500mg)流速流速8 81010ml/minml/min收集洗脱液收集洗脱液6ml(6ml(丙酮丙酮:甲甲酸酸10001000:1)1)N N2 2 吹干吹干定溶至定溶至1ml1ml上机上机加入氨水调节加入氨水调节pH=7pH=724BeijingSWTP2SWTP1SWTP4SWTP3R1R2R5R4R3R6Nanshahe RiverLocation of 4 SWTPs and sampling si

36、te of receiving riversBeijing ZRZY JD WRR1R2R5R4R3R6Nanshahe River25环境样品检测结果环境样品检测结果资源资源（ng/L）中瑞中瑞（ng/L）五肉联五肉联（ng/L）大红门大红门（ng/L）进水进水 出水出水 进水进水 出水出水 进水进水 出水出水 进水进水 出水出水磺胺磺胺53054144626376579473磺胺对甲氧磺胺对甲氧嘧啶嘧啶672949139630283磺胺氯哒酮磺胺氯哒酮92722911134磺胺喹啉磺胺喹啉005611471541磺胺类磺胺类26资源（资源（ng/L）中瑞（中瑞（ng/L）五肉联五肉联（ng

37、/L）大红门大红门（ng/L）进水进水出水出水进水进水出水出水进水进水出水出水进水进水出水出水 氧氟沙星氧氟沙星 208 73 153 74 198 74 288 123 环丙沙星环丙沙星 109 23 23 11 141 70 72 8 培氟沙星培氟沙星 51 15 59 28 23 7 29 5 诺氟沙星诺氟沙星 55 14 33 19 50 28 41 6 恩诺沙星恩诺沙星 59 13 116 52 87 21 83 21 洛美沙星洛美沙星 13 3 6 2 10 2 10 1 喹诺酮类喹诺酮类27资源资源（ng/L）中瑞中瑞（ng/L）五肉联五肉联（ng/L）大红门大红门（ng/L）进

38、水进水出水出水进水进水出水出水进水进水出水出水进水进水出水出水四环素四环素50519319733316454718土霉素土霉素4295085450970920877031红霉素红霉素180182111042055923913吉他霉素吉他霉素16617191941875521712泰勒菌素泰勒菌素15317177871695019611四环素类和大环内酯类四环素类和大环内酯类28其它类其它类 资源资源（ng/L）中瑞中瑞（ng/L）五肉联五肉联（ng/L）大红门大红门（ng/L）进水进水出水出水进水进水出水出水进水进水出水出水进水进水出水出水安定安定165151261282413726氯霉素氯霉

39、素n.dn.d125n.dn.dn.dn.d克伦特罗克伦特罗42n.dn.d8331美托洛尔美托洛尔61212120229南沙河南沙河PPCPsPPCPs存在水平存在水平Beijing ZRZY JD WRR1R2R5R4R3R6Nanshahe River30环境污水和污泥中抗性激素药物检测方环境污水和污泥中抗性激素药物检测方法研究法研究31研究背景研究背景近年来，关于环境内分泌干扰物近年来，关于环境内分泌干扰物（Endocrine Disrupting Chemicals,EDCsEndocrine Disrupting Chemicals,EDCs）的研究已引起世界各国的广泛关注。的研究

40、已引起世界各国的广泛关注。全球全球抗性激素药物消耗量增长迅速：激抗性激素药物消耗量增长迅速：激素依赖型疾病如乳腺癌和前列腺癌等疾素依赖型疾病如乳腺癌和前列腺癌等疾病发病率逐渐升高。病发病率逐渐升高。多氯联苯多氯联苯有机锡有机锡烷基酚烷基酚激素类等激素类等环境中的抗性激素药物环境中的抗性激素药物 32抗性激素药物抗性激素药物性性激激素素雌激素雌激素孕激素孕激素雄激素雄激素抗雄激素抗雄激素抗孕激素抗孕激素抗雌激素抗雌激素雌激素受体拮抗剂雌激素受体拮抗剂(他莫昔芬、托瑞米芬他莫昔芬、托瑞米芬)芳香酶抑制剂芳香酶抑制剂（来曲唑、阿那曲唑）（来曲唑、阿那曲唑）雄激素受体阻滞剂雄激素受体阻滞剂（色普龙、氟

41、他胺）（色普龙、氟他胺）5-5-还原酶抑制剂还原酶抑制剂（非那雄胺）（非那雄胺）（米非司酮）（米非司酮）33抗性激素药物生态毒理效应抗性激素药物生态毒理效应34抗性激素药物分析现状抗性激素药物分析现状其他抗性激素药物其他抗性激素药物？35研究内容研究内容建立环境介质（污水、污泥）中典型抗建立环境介质（污水、污泥）中典型抗性激素药物的液相质谱（性激素药物的液相质谱（LC-MS/MSLC-MS/MS）的同时分析方法的同时分析方法采集北京市医院废水样品、北京市主要采集北京市医院废水样品、北京市主要污水处理厂进出水和污泥样品，检测目污水处理厂进出水和污泥样品，检测目标药物在这些样品中的存在水平标药物在

42、这些样品中的存在水平 36目标药物理化性质目标药物理化性质37Logkow:2.4-6.8pKa:1.63-14.238水体介质中抗性激素药物分析方法的建水体介质中抗性激素药物分析方法的建立立u仪器参数仪器参数u前处理方法前处理方法u方法的应用方法的应用39仪器参数仪器参数质谱条件质谱条件电离方式：电离方式：ESI+毛细管电压：毛细管电压：3.5 kV 离子源温度：离子源温度：100C脱溶剂温度：脱溶剂温度：450 C 脱溶剂气流量：脱溶剂气流量：600 L/h碰撞腔真空度：碰撞腔真空度：3.010-3 mbar 多反应监测模式多反应监测模式 MRM4016hunbiao25ppb ACN:W

43、ATER0.30Time1.002.003.004.005.006.007.008.009.0010.00%010020081025545:MRM of 15 Channels ES+TIC7.99e62.7816hunbiao25ppb 0.1%FA:ACN0.30Time1.001.502.002.503.003.504.004.505.005.506.006.507.00%010020081025615:MRM of 15 Channels ES+TIC2.87e62.7516hunbiao25ppb 0.1%FA:MeOH0.30Time1.001.502.002.503.003.50

44、4.004.505.005.506.006.507.00%010020081025585:MRM of 15 Channels ES+TIC1.97e63.8216hunbiao25ppb MeOH:WATER0.30Time1.002.003.004.005.006.007.008.009.0010.00%010020081025565:MRM of 15 Channels ES+TIC2.76e63.85甲醇甲醇-水水乙腈乙腈-水水甲醇甲醇-0.1%-0.1%甲酸水甲酸水乙腈乙腈-0.1%-0.1%甲酸水甲酸水41液相梯度条件液相梯度条件42MRM色谱图色谱图43前处理前处理HLB、GCB

45、、C18HLBHLBC18:pH2、5GCB:pH没有影响没有影响44HLB 90%HLB 90%HLBHLB、C18C18和和GCB GCB 对目标化合物回收率比较对目标化合物回收率比较HLB,pH 2HLB,pH 245基质抑制效应基质抑制效应 以污水处理厂进水为例以污水处理厂进水为例0.020.040.060.080.0100.0120.0雷洛昔芬来曲唑阿那曲唑米非司酮依西美坦非那雄胺去甲基他莫昔芬托瑞米芬克罗米芬他莫昔芬目标药物基质抑制率（%）HLB+NH2HLB60%NH2净化后，绝大部分药物净化后，绝大部分药物88%88%PCX（阳离子交换柱阳离子交换柱）HLBHLB（亲水亲脂平衡

46、柱）（亲水亲脂平衡柱）57基质抑制基质抑制PCX 40%PCX 308.0455.0,174.6,308.02030硫唑嘌呤277.9141.9277.9,141.9,231.91125多柔比新544.3397.0544.3,129.7,397.01218多柔比新醇546.0399.1546.0,363.0,399.11317环磷酰胺 260.9140.0260.9,140.0,105.62030异环磷酰胺260.992.1260.9,92.1,153.52427长春新碱825.4765.4825.4,765.4,807.63770依托泊苷589.0229.1589.0,229.1,435.1

47、1420甲基苄肼221.9179.9221.9,162.5,179.9142571方法验证（污水处理厂进水）化合物线性范围(ng/mL)相关系数(r2)加标回收率 20 ng/L(RSD,%)n=5加标回收率 200 ng/L(RSD,%)n=5检出限(ng/L)定量限(ng/L)甲氨蝶呤1.002000.998461(2)67(5)0.61.7硫唑嘌呤2.502000.9992102(3)95(3)1.65.0多柔比新醇10.04000.999566(11)72(4)6.520.0多柔比新10.04000.997970(11)68(5)6.520.0环磷酰胺1.252000.999093(6

48、)96(10)0.82.5异环磷酰胺5.002000.999880(12)80(17)2.57.0长春新碱10.04000.999851(21)56(13)7.020.0依托泊苷8.003200.998797(8)99(7)5.015.0甲基苄肼8.003200.9981104(7)98(6)5.516.072方法验证方法验证 （污水处理厂出水）（污水处理厂出水）化合物线性范围(ng/mL)相关系数(r2)加标回收率 20 ng/L(RSD,%)n=5加标回收率 200 ng/L(RSD,%)n=5检出限(ng/L)定量限(ng/L)甲氨蝶呤1.002000.994261(5)57(5)0.6

49、1.7硫唑嘌呤1.252000.9992100(10)91(6)1.23.5多柔比新醇2.504000.999270(7)71(3)1.65.0多柔比新2.504000.998668(8)67(3)2.56.5环磷酰胺0.632000.9967109(6)96(4)0.51.5异环磷酰胺2.502000.997792(4)83(4)1.65.0长春新碱5.004000.998645(25)50(6)3.510.0依托泊苷4.003200.998095(10)91(4)2.57.0甲基苄肼4.003200.9991106(4)100(4)2.68.073基质效应基质效应 a a化合物进水(RSD

50、,%)n=5出水(RSD,%)n=5HLBHLB+WAXHLBHLB+WAX甲氨蝶呤187(6)217(6)169(4)93(3)硫唑嘌呤17(11)42(9)23(7)63(6)多柔比新醇n.d.b22(10)6(13)42(6)多柔比新n.d.b25(7)6(10)43(8)环磷酰胺20(9)36(6)47(7)64(7)异环磷酰胺30(11)48(6)54(5)74(8)长春新碱n.d.b82(3)215(7)146(4)依托泊苷5(7)22(6)12(8)42(9)甲基苄肼17(8)25(8)39(6)65(4)a 基质效应基质效应=(基质加标曲线斜率基质加标曲线斜率/溶剂加标曲线斜率