16第十六章药品质量控制中的现代分析方法与技术.pptx

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1、药品质量控制中的药品质量控制中的现代分析方法与技术现代分析方法与技术Modern analytical methods & techniquesin quality control of drugs第十六章第十六章 现代分析方法与技术，为药学的发展提供了适时而有效的现代分析方法与技术，为药学的发展提供了适时而有效的手段与动力。手段与动力。色谱及其联用技术：色谱及其联用技术： 药学研究分子水平。药学研究分子水平。手性分析：手性分析： 毛细管电泳及手性色谱技术药物研究毛细管电泳及手性色谱技术药物研究与质量控制提供了保障。与质量控制提供了保障。现代光谱技术：现代光谱技术： 药物结构鉴定，药物结构鉴定

2、， 微量杂质检定。微量杂质检定。第一节 概况Capillary electrophoresis,CEModern chromatogr & its application药物现代色谱法及其应用药物现代色谱法及其应用UPLCUltraPerformance LC (UPLC ) technology starts with unique 1.7 m small-particle chemistries. Chromatographers no longer need to choose between speed and resolutionwith UPLC you get both.Mass

3、 spectroscopy MSNuclear magnetic resonance spectrometry NMRX-ray diffraction methodNear infrared spectrometry NIRS现代光谱法及其应用现代光谱法及其应用Modern spectroscopy & its application in pharmaceutical analysisGC-FTIRGC-MSUPLC-MSHPLC-NMRHyphenated Techniques in Chromatography 现代联用技术及其应用现代联用技术及其应用HPLC-MSCE-MS+样品与溶

4、剂脱离及电离 EI ESI APCILC/MS接口离子源质量分析器检测离子HPLC数据系统离子识别 Quadrapole Time of Flight Fourier Transform +离子检测+-+-+第二节第二节 液质联用技术与应用液质联用技术与应用2.1 离子化方式离子化方式2.2 离子分离与测定模式离子分离与测定模式Full-Scan Mass Spectrometry Advantage Provides MW InformationFull-Scan MS of BuspironeNNNNNOOBuspirone (丁螺环酮)C21H31N5O2MW = 38515020025

5、0300350400450500m/z255075100Relative Abundance386408(M+H)+(M+Na)+Single Ion Monitoring (SIM) Advantages Targeted Analyte Monitoring High Duty Cycle Simple Disadvantages Can suffer from interferences Not as sensitive or selective as SRM (see below)Fixed m/zPass AllPass AllProduct Ion Scanning: A Tand

6、em MS Method Advantage Provides Structural Information Disadvantage Low duty cycleFixed m/zPass AllScanningProduct Ion SpectrumQ3Q2Q1Product Ion Spectrum of BuspironeNHNNNOONHNOO100150200250300350400m/z255075100Relative Abundance122386222150265180NNNNHNOO(M+H)+Precursor Ion ScanningAdvantage ID comp

7、ounds producing specific fragment ion (e.g., PO3 for phosphopeptides)Disadvantage Low duty cycleFixed m/zPass AllScanningPrecursor Ion SpectrumQ3Q2Q1Precursor Ion Scan Mode for Buspirone MetabolitesPrecursor Ion Scan: Q3 set to m/z 122NNNNNOOOH100200300400500m/zRelative Abundance40238691011121314151

8、6Time (min)255075100Relative Abundance11.6213.8413.1614.4012.1310.4515.45NNNNNOONHNNNeutral Loss Scanning Advantage Screen for compounds producing specific neutral loss (e.g., loss of 176 for glucuronide conjugates) Disadvantage Low duty cycleScanningPass AllScanningNeutral Loss SpectrumLinkedQ3Q2Q1

9、Neutral Loss Scan of Buspirone MetabolitesNeutral Loss Scan: Q1/Q3 difference set to 121 Da100200300400500m/zRelative Abundance402386910111213141516Time (min)255075100Relative Abundance13.9211.6913.2115.5010.58NNNNNOONNNNNOOOHSelected Reaction Monitoring (SRM) Advantages Targeted Analyte Monitoring

10、High Duty Cycle “Simultaneous” Monitoring of Multiple Transitions Disadvantage No “advanced” structural informationFixed m/zPass AllFixed m/zQ1Q2Q3MS/MS Selectivity in Complex Matrices息斯敏阿斯咪唑(astemizole) Chlroamphenicol(氯霉素，氯霉素，CAP)残留测定残留测定 黄杨生物碱成分鉴定黄杨生物碱成分鉴定 苯甲酸利扎曲普坦人体药代动力学研究苯甲酸利扎曲普坦人体药代动力学研究2.3药物分

11、析中的典型应用药物分析中的典型应用OHOHNHHHOClClO2NC11H12Cl2N2O5FMW=323.13【类别】酰胺醇类抗生素【适应症】本品是治疗伤寒、副伤寒的首选药物，外用可治疗沙眼。因脑脊液浓度高，故常用于治疗细菌性脑膜炎和脑脓肿。此外，尚可外用治疗痤疮、酒糟鼻、脂溢性皮炎等。 被农业养殖滥用！ 肉食品中严格检查。2.3.1 Chlroamphenicol(氯霉素，氯霉素，CAP)残留测定残留测定HPLC analysis was performed on the Finnigan Surveyor HPLC module with MS Pump and AutosamplerC

12、olumn: Thermo Hypersil Gold C18 (1002.1 mm, 5)Mobile Phase: A: Water; B: AcetonitrileColumn Temperature: 40 oCGradient Program: 0.25 mL/minInjection: 20 uL with loopTime (min)% A% B080202.520803.020803.180205.08020Operation Conditions for CAPIon source:ESIIon polarity:NegativeSpray voltage:4000 VShe

13、ath gas pressure:45Auxiliary gas pressure:15Ion transfer capillary temperature:300 oCSource CID:8 VScan Type:SRM, 3 transitions of M-H-(m/z: 321)(321152, 321 194 and 321 257)Q1 peak width0.7 Da in SRM or 0.2 Da in H-SRMQ3 peak width0.7 DaCollision Pressure:Ar at 1.3 mTorrOHOHNHHHOClClO2NQ1 peak widt

14、h and H-SRM experiment Enabling the H-SRM experiment Highly Selective Selected Reaction Monitoring (H-SRM) Reduces “isobaric” chemical noise Increases confidence of analysis & improved LOQQ1 peak width0.7 Da in SRM or 0.2 Da in H-SRMQ3 peak width0.7 DaOHOHNHHOClClO2NONHHNOClClOHONHHHOClClO2NOHO2NOHC

15、O2NOHHm/z 321m/z 257m/z 321m/z 194m/z 152CAP SRM Result: CAP Standard Q1 peak width = 0.7 DaRT: 0.00 - 5.000.00.20.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance020406080100RT: 2.83AA: 60868SN: 15803.843.254.652.341

16、.030.802.473.561.530.324.523.113.431.731.880.172.064.872.644.170.644.311.230.471.402.20RT: 2.83AA: 23577SN: 16694.653.201.032.133.793.574.213.392.373.970.114.421.400.834.901.692.541.890.680.310.461.241.53RT: 2.83AA: 13035SN: 1644RT: 2.83AA: 24218SN: 6393.843.252.341.030.802.474.593.564.761.530.323.1

17、13.431.734.431.880.172.062.644.174.311.230.541.402.20NL:1.82E4TIC F: MS ICIS 1221C03NL:7.07E3Base Peak m/z= 151.50-152.50 F: MS ICIS 1221C03NL:4.48E3Base Peak m/z= 193.50-194.50 F: MS ICIS 1221C03NL:6.77E3Base Peak m/z= 256.50-257.50 F: MS ICIS 1221C03TIC321-152321-194321-257CAPPeak Area Counts = 2.

18、4E4CAP SRM Result: Kidney Blank RT: 0.00 - 5.000.00.20.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance0204060801001.281.481.751.892.052.612.231.032.832.462.953.073.223.783.480.694.603.624.324.060.364.870.184.454.720.

19、512.772.052.231.851.641.522.421.772.572.953.253.351.313.544.321.034.163.974.870.420.930.224.723.824.463.690.811.180.662.152.682.991.651.852.293.212.831.372.392.033.524.504.013.673.451.124.610.194.924.324.200.940.420.820.691.281.481.751.892.612.052.231.032.462.833.073.293.783.490.694.603.624.060.364.

20、374.214.830.180.51NL:5.30E4TIC F: MS 1221D05NL:1.79E3Base Peak m/z= 151.50-152.50 F: MS 1221D05NL:4.69E2Base Peak m/z= 193.50-194.50 F: MS 1221D05NL:5.27E4Base Peak m/z= 256.50-257.50 F: MS 1221D05TIC321-152321-194321-257CAP SRM Result: Kidney Spiked (0.5ng/g)RT: 0.00 - 5.000.00.20.40.60.81.01.21.41

21、.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance0204060801001.292.061.482.881.842.262.421.082.762.623.033.343.483.973.624.943.784.814.390.580.130.464.240.280.774.104.66RT: 2.88AA: 13715SN: 30RMS2.231.572.111.452.451.821.283.342.593.48

22、3.933.191.124.163.710.694.390.434.710.190.870.554.864.54RT: 2.88MA: 6787SN: 17RMS2.511.882.661.661.081.261.972.261.473.820.950.724.123.033.204.673.654.403.374.854.543.980.550.330.134.26RT: 2.87MA: 14653SN: INF1.292.061.481.842.291.002.422.613.033.253.393.973.624.943.784.814.390.580.130.464.240.280.7

23、74.104.66NL:4.68E4TIC F: MS 1221D08NL:3.47E3Base Peak m/z= 151.50-152.50 F: MS ICIS 1221D08NL:2.26E3Base Peak m/z= 193.50-194.50 F: MS 1221D08NL:4.63E4Base Peak m/z= 256.50-257.50 F: MS 1221D08TIC321-152321-194321-257CAPNot accurate for confirmationCAP detectedCAP H-SRM Result: CAP Standard Q1 peak

24、width = 0.2 DaRT: 0.00 - 5.000.00.20.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance020406080100RT: 2.89AA: 16306SN: 1762RMS1.661.780.221.153.864.324.893.462.031.010.551.512.302.614.593.311.320.773.083.680.363.994.20

25、2.732.444.724.442.15RT: 2.89AA: 7313SN: 24498RMS3.423.083.854.384.831.073.980.151.331.532.061.763.673.301.932.560.362.200.492.694.120.690.884.592.36RT: 2.91AA: 1841SN: 273RMSRT: 2.89AA: 7129SN: 768RMS1.661.780.221.154.323.863.461.012.030.552.301.512.614.593.311.324.870.773.680.364.202.444.003.074.72

26、4.46NL:5.46E3TIC F: MS ICIS 1221G11NL:2.39E3Base Peak m/z= 151.50-152.50 F: MS ICIS 1221G11NL:7.50E2Base Peak m/z= 193.50-194.50 F: MS ICIS 1221G11NL:2.46E3Base Peak m/z= 256.50-257.50 F: MS ICIS 1221G11TIC321-152321-194321-257Peak Area Counts = 7.3E3CAP H-SRM Result: Kidney BlankRT: 0.00 - 5.000.00

27、.20.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance0204060801001.301.782.051.952.591.471.012.412.201.672.853.220.290.520.733.504.643.864.320.863.330.114.114.894.774.443.691.521.623.111.871.432.264.641.774.320.953.332

28、.832.550.751.214.843.560.454.150.580.193.854.544.013.731.133.862.732.922.580.222.461.621.502.060.991.292.351.724.373.371.420.670.802.224.690.481.850.144.093.103.244.943.563.731.301.782.051.952.591.471.012.412.202.853.220.290.520.733.503.110.860.114.114.624.894.233.863.694.41NL:2.08E3TIC F: MS 1221G0

29、4NL:2.14E2Base Peak m/z= 151.50-152.50 F: MS 1221G04NL:2.70E1Base Peak m/z= 193.50-194.50 F: MS 1221G04NL:2.06E3Base Peak m/z= 256.50-257.50 F: MS 1221G04TIC321-152321-194321-257No CAP detectedCAP H-SRM Result: Kidney Spiked (0.5ng/g)RT: 0.00 - 5.000.00.20.40.60.81.01.21.41.61.82.02.22.42.62.83.03.2

30、3.43.63.84.04.24.44.64.8Time (min)020406080100020406080100020406080100Relative Abundance020406080100RT: 2.86MA: 7799SN: 23841.302.052.581.581.832.202.340.991.172.990.813.144.893.680.313.293.960.094.490.573.414.264.703.554.13RT: 2.85AA: 2757SN: 274RMS2.061.461.651.921.292.241.112.641.773.293.964.492.

31、404.934.700.983.783.093.554.130.530.800.300.144.330.67RT: 2.85AA: 1107SN: 240RMS1.564.891.661.382.362.191.05 1.172.042.604.430.163.333.493.103.992.724.133.861.863.640.794.260.534.780.390.674.60RT: 2.86MA: 3554SN: 1NL:2.45E3TIC F: MS 1221G07NL:8.97E2Base Peak m/z= 151.50-152.50 F: MS ICIS 1221G07NL:3

32、.82E2Base Peak m/z= 193.50-194.50 F: MS ICIS 1221G07NL:2.39E3Base Peak m/z= 256.50-257.50 F: MS 1221G07TIC321-152321-194321-257CAP2.3.2 黄杨宁生物碱黄杨宁生物碱HPLC-MS联用鉴定联用鉴定黄杨科植物小叶黄杨Buxus microphlla Sieb. et. Zucc. var. sinica Rehd.et Wils中含有具有较强心血管疾病治疗活性的孕甾烷生物碱，主要含环维黄杨星D、环黄杨碱D和环常绿黄杨碱C等生物碱成分。 黄杨生物碱HPLC-ELSD色谱

33、图 色谱条件色谱条件色谱柱：Lichrospher SiO2 (250mm4.6mm,5 m)流动相：四氢呋喃-甲醇-乙腈-氨水 ( 32:50:13:3)流速：1mLmin -1柱温：30ELSD参数：漂移管温度70 雾化气体（N2） 流速：1.5 Lmin -1环维黄杨星D和有关生物碱含量测定结果次数环维黄杨星D含量% 峰1生物碱含量%峰2生物碱含量%峰4生物碱含量%峰5生物碱含量%有关生物碱总含量% 186.853.578.090.790.9213.37287.083.848.540.800.9814.15385.833.468.820.810.9514.03485.703.548.76

34、0.870.9314.10585.053.528.640.740.8513.75684.843.749.030.790.9714.53Mean85.893.618.650.800.9313.99RSD%1.073.653.384.624.632.8环维黄杨星环维黄杨星D及其有关生物碱的鉴别及其有关生物碱的鉴别 质谱条件 电喷雾离子化正离子检测 喷口电压5000V 雾化气压35psi 辅助气压力5psi 毛细管温度350 碰撞气氩气压力1.5mTorr 色谱条件 色谱柱：Lichrospher SiO2 (250mm4.6mm,5 m) 流动相：四氢呋喃-甲醇-乙腈-氨水 ( 32:50:13:

35、3) 流速：1mLmin -1 柱温：30黄杨宁LC-MS/MS全扫描色谱图 黄杨宁LC-MS/MS全扫描色谱放大图 123456789峰1母离子质荷比峰1二级质谱图M+H+=370可能为峰1的黄杨宁有关生物碱NOCH3CH3NCH3CH3HOCH3HONHNHOCH3Cyclobuxomicreine KCyclobuxosuffrine KBuxenone MCyclobuxoviridine B峰2母离子质荷比峰2二级质谱图M+H+= 431可能为峰2的黄杨宁有关生物碱NNHCH3CH2OHCH3CH3OHNONHCH3CH2OHCH3CH3NOHNOCH3CH3CH3NCH3CH2OH

36、CH3OHNHCH3Cyclomicrophylline BBuxazidine BCyclobuxoxazine CCyclomicrophylline C峰3母离子质荷比峰3二级质谱图M+H+= 415可能为峰3的黄杨宁有关生物碱NNCH3CH3CH3CH3NNHCH3CH3OHCH3NNHCH3CH3OHCH3NHNCH3CH2OHCH3CH3Cycloprotobuxine ACyclokreanine BCyclovirobuxeine B16-deoxybuxidienine C峰4母离子质荷比峰4二级质谱图CH3CH3NHCH3CH3OHNHCH3HCH3HCH3CH3环常绿黄杨

37、碱CM+H+= 417峰5母离子质荷比峰5二级质谱图M+H+= 401383.34可能为峰5的黄杨宁有关生物碱NCH3CH3CH3NHNH2CH3OHNCH3NCH3CH3CH3NCH3CH3CH3NCH3CH2NHOHCycloprotobuxine CBuxaminol EBuxocyclamine ACyclobuxine B峰6母离子质荷比峰6二级质谱图NHCH3CH3OHNHCH3HCH3HCH3CH2环黄杨碱DM+H+= 387峰7母离子质荷比峰7二级质谱图CH3CH3NHCH3CH3OHNHCH3HCH3HCH3环维黄杨星DM+H+= 403峰8母离子质荷比M+H+= 375 3

38、57.15峰8二级质谱图峰9二级质谱图 371.17CH3OHNH2CH3HCH3HCH3CH3NH2H2OCH3NH2CH3HCH3HCH3CH3NH2CH3OHHCH3HCH3CH3NH2CH3HCH3HCH3CH3NH2CH3HCH3HCH3CH3NH2CH3H2ONH3m/z=375m/z=357m/z=344m/z=326m/z=309 357.15NHCH3CH3OHNHCH3HCH3HCH3CH2峰9母离子质荷比M+H+= 389NHCH3CH3OHNHCH3HCH3HCH3CH3峰9二级质谱图 371.17NHCH3CH3OHNH2CH3HCH3HCH3CH3H2ONHCH3N

39、H2CH3HCH3HCH3CH3NH2CH3NHCH3OHHCH3HCH3CH3H2ONHCH3CH3HCH3HCH3CH3NH2CH3CH3HCH3HCH3CH3m/z=389m/z=371m/z=358m/z=340m/z=309 371.17峰位号tR(min)M+H+(m/z)特征碎片离子(m/z)可能生物碱名称13.92370339，325，283，135，70，58Cyclobuxomicreine K, Cyclobuxosuffrine K,Buxenone M, Cyclobuxoviridine B24.03431413，382，323，86，70，58Buxazidine

40、 B, Cyclomicrophylline B,Cyclobuxoxazine C, Cyclomicrophylline C35.35415384，84，58Cycloprotobuxine A,Cyclokreanine B,Cyclovirobuxeine B, 16-deoxybuxidienine C45.92417399，386，368，84，58Cylcyclovirobuxine C56.11401370，352，326，171，58Cycloprotobuxine C, Buxaminol E,Buxocyclamine A, Cyclobuxine B67.0338736

41、9，356，338，171，58Cyclobuxine D77.63403385，372，354，70，58Cyclovirobuxine D88.28375357，344，326，309，58未有相关文献报道99.77389371，358，340，173，70，58可能为Cyclobuxine D双键加氢还原产物HPLC-ELSD法黄杨宁有关生物碱归属表NNNNHN*.COOH苯甲酸利扎曲普坦苯甲酸利扎曲普坦 (Rizatriptan Benzoate) MW: 391.47 分子式分子式：C15H19O5C7H6O25-HT受体拮抗剂受体拮抗剂2.3.3 苯甲酸利扎曲普坦人体药代动力学研究

42、苯甲酸利扎曲普坦人体药代动力学研究药理作用v 刺激大脑血管壁的后接点5-HT1B受体收缩血管，降低颅内血管通透性；v 刺激三叉神经前突触5-HT1D受体，调节神经递质的释放，抑制硬膜的神经原性炎症反应和血浆外渗；v 阻止血管肽的释放，使血管口径正常化，通过收缩颅内血管并抑制神经炎症； v 刺激脑干5-HT1B或5-HT1D受体，抑制三叉神经核兴奋； v 减少颈动脉血流； v 透过血脑屏障，增加脑血流量。 实验内容v 建立苯甲酸利扎曲普坦在血浆、尿样浓度的LC-MS/MS测定方法v 苯甲酸利扎曲普坦分散片和胶囊进行生物等效性试验v 苯甲酸利扎曲普坦片体内药代动力学研究 单剂量 (5,10,15

43、mg) 多次给药(10 mg) 稳态(10 mg)LC-MS/MS测定方法建立测定方法建立v 测定方法选择测定方法选择v 质谱条件优化质谱条件优化v 色谱条件选择色谱条件选择 色谱柱选择色谱柱选择 缓冲盐选择缓冲盐选择v 血浆处理方法血浆处理方法 液液萃取法液液萃取法 蛋白沉淀法蛋白沉淀法v 内标选择内标选择LC-MS/MSm/z 270m/z 158Phenomenx PFP1%冰醋酸冰醋酸, 0.2%醋酸铵醋酸铵蛋白沉淀法蛋白沉淀法盐酸曲马多盐酸曲马多色谱条件色谱条件流动相A：醋酸盐缓冲液(1%冰醋酸，2%醋酸铵;pH 3.5)流动相B：甲醇(0.1%甲酸)梯度条件过程：0 min (B5

44、0%)1.0 min (B95%)4.5 min (B95%)4.6 min (B50%) 6.5 min (B50%)空白溶剂色谱图 预处理的空白血浆色谱图 RT: 0.00 - 6.500246Time (min)020406080100020406080100Relative AbundanceNL:1.00E5TIC F: + c sid=-12.00 SRM ms2 263.90-20.00 57.99-58.00 MS washNL:1.00E3TIC F: + c sid=-12.00 SRM ms2 269.90-20.00 158.10 MS washRT: 0.00 - 6

45、.500246Time (min)020406080100020406080100Relative AbundanceNL: 1.00E5TIC F: + c sid=-12.00 SRM ms2 263.90-20.00 57.99-58.00 MS M-Cline-4-01NL: 1.00E3TIC F: + c sid=-12.00 SRM ms2 269.90-20.00 158.10 MS M-Cline-4-01质谱条件质谱条件离子检测方式： ESI+ SRM检测对象： 利扎曲普坦 m/z 269.9158.1 曲马多 m/z 263.958.0喷口电压： 5000 V雾化气压：

46、35 psi辅助气压力： 5 psi毛细管温度： 350碰撞气氩气压力： 1.3mTorr碰撞能量： 20 eV质谱条件优化质谱条件优化LZQPT #2385 RT: 20.83 AV: 1 NL: 1.95E5T: + c sid=-8.00 Q3MS 170.00-350.00180200220240260280300320340m/z0102030405060708090100Relative Abundance270.14187.02274.25340.23241.02318.24286.14228.01301.03346.26247.05182.08222.04262.24312.2

47、5205.97288.09328.17利扎曲普坦LC-MS质谱扫描图（m/z =270） LZQPT #2994 RT: 26.34 AV: 1 NL: 3.60E5T: + c sid=-8.00 Full ms2 270.00-25.00 50.00-350.0050100150200250300350m/z0102030405060708090100Relative Abundance158.0358.10201.08155.92172.00225.03129.9490.86270.5159.24332.51314.94利扎曲普坦LC-MS/MS质谱扫描图（m/z=158） NNNNHN

48、6844NHm/z 270m/z 158利扎曲普坦质谱裂解图 m/z 270m/z 158 （碰撞能量：20ev）色谱条件选择色谱条件选择色谱柱色谱柱Intersil-ODS C18Lichrospher-C18 Zorbak-ODS C18 Lichrospher-CN Phenomenx Curosil-PFP 缓冲盐条件(0.1%HCOOH,v/v; 0.2%醋酸铵,w/v; pH3.0）采用PFP（五氟苯基）五氟苯基）柱柱，样品的保留适当，峰型良好，有机相和水相的比例也较为适当。醋酸铵(w/v)0.05%0.1%0.2%甲醇:水=(50:50)0.2% (w/v)醋酸铵样品峰响应高，拖

49、尾得到一定程度的改善。0.1% HCOOH0.1% HAC0.2% HAC 0.5% HAC 1.0% HAC1%HAC水相pH值为3.5，样品保留时间合适，峰形良好。 血浆处理方法血浆处理方法苯甲酸利扎曲普坦血浆提取条件试验 内标选择内标选择OHNOHNN佐米曲普坦佐米曲普坦 (Zolmitriptan) MW：287 分子式：分子式：C16H21N3O2HONCH3H3COCH3.HCl盐酸曲马多盐酸曲马多 (Tramadol hydrochloric) MW：299.8 分子式：分子式：C16H25NO2tmd #176 RT: 3.03 AV: 1 SB: 81 0.55-1.93 N

50、L: 2.03E6T: + c sid=-10.00 Q3MS 50.00-350.0050100150200250300350m/z0102030405060708090100Relative Abundance264.10157.99125.99288.93320.26165.98256.1860.05302.06348.89218.97190.9890.92116.94曲马多LC-MS质谱扫描图（m/z=264） tmd #3619-4202 RT: 14.32-16.85 AV: 565 NL: 9.20E5T: + c sid=-12.00 Full ms2 263.90-25.00