【文档说明】药物分析课件第六版第十六章药品质量控制中的现代分析方法与技术.ppt，共(90)页，3.774 MB，由小橙橙上传

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Capillaryelectrophoresis,CEModernchromatogr&itsapplication药物现代色谱法及其应用UPLCUltraPerformanceLC®(UPLC®)technologys

tartswithunique1.7µmsmall-particlechemistries.Chromatographersnolongerneedtochoosebetweenspeedandresolution—withUPLCyougetb

oth.MassspectroscopyMSNuclearmagneticresonancespectrometryNMRX-raydiffractionmethodNearinfraredspectrometryNIRS现代光谱法及其应用Moderns

pectroscopy&itsapplicationinpharmaceuticalanalysisGC-FTIRGC-MSUPLC-MSHPLC-NMRHyphenatedTechniquesinChromatography现代联用技术及其应用HPLC-MSCE-MS+

+样品与溶剂脱离及电离EIESIAPCILC/MS接口离子源质量分析器检测离子HPLC数据系统质谱离子识别QuadrapoleTimeofFlightFourierTransform…+++++++离子检测++-++++++-+++第二节液质联用技术与应用2.1离子化方式2.2离子

分离与测定模式Full-ScanMassSpectrometry•Advantage–ProvidesMWInformationFull-ScanMSofBuspironeNNNNNOOBuspirone(丁螺环酮)C21H31N5O2MW=385150200250300350400450500

m/z255075100RelativeAbundance386408(M+H)+(M+Na)+SingleIonMonitoring(SIM)•Advantages–TargetedAnalyteMonitoring–HighDutyCycle–Si

mple•Disadvantages–Cansufferfrominterferences–NotassensitiveorselectiveasSRM(seebelow)Fixedm/zPassAllPassAllProductIonScanning:AT

andemMSMethod•Advantage–ProvidesStructuralInformation•Disadvantage–LowdutycycleFixedm/zPassAllScanningProductIonSpectrumQ3Q2Q1ProductIonSpectrumof

BuspironeNHNNNOONHNOO100150200250300350400m/z255075100RelativeAbundance122386222150265180NNNNHNOO(M+H)+PrecursorIonScanning•Advantage–I

Dcompoundsproducingspecificfragmention(e.g.,PO3−forphosphopeptides)•Disadvantage–LowdutycycleFixedm/zPassAllScanningPrecursor

IonSpectrumQ3Q2Q1PrecursorIonScanModeforBuspironeMetabolitesPrecursorIonScan:Q3settom/z122NNNNNOOOH100200300400500m/zRelativeAbundance

402386910111213141516Time(min)255075100RelativeAbundance11.6213.8413.1614.4012.1310.4515.45NNNNNOONHNNNeu

tralLossScanning•Advantage–Screenforcompoundsproducingspecificneutralloss(e.g.,lossof176forglucuronideconjugates)•

Disadvantage–LowdutycycleScanningPassAllScanningNeutralLossSpectrumLinkedQ3Q2Q1NeutralLossScanofBuspironeMetabolitesNeutralLossScan:Q1/Q3difference

setto121Da100200300400500m/zRelativeAbundance402386910111213141516Time(min)255075100RelativeAbundance13.9211.6913.2115.5010.58NNN

NNOONNNNNOOOHSelectedReactionMonitoring(SRM)•Advantages–TargetedAnalyteMonitoring–HighDutyCycle–“Simultaneous”MonitoringofMultipleTr

ansitions•Disadvantage–No“advanced”structuralinformationFixedm/zPassAllFixedm/zQ1Q2Q3MS/MSSelectivityinComplexMatrices息斯敏——阿斯咪唑(astemizole)•Chlroam

phenicol(氯霉素，CAP)残留测定•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2.3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

。2.3.1Chlroamphenicol(氯霉素，CAP)残留测定HPLCanalysiswasperformedontheFinniganSurveyorHPLCmodulewithMSPumpandAutosampler–Column:ThermoHypersilGol

dC18(100×2.1mm,5µ)–MobilePhase:A:Water;B:Acetonitrile–ColumnTemperature:40oC–GradientProgram:0.25mL/min–Injection:20uLwithloopTime(min)%A%B08

0202.520803.020803.180205.08020OperationConditionsforCAPIonsource:ESIIonpolarity:NegativeSprayvoltage:4000VSheathgaspressure:45Auxiliarygaspressure:

15Iontransfercapillarytemperature:300oCSourceCID:8VScanType:SRM,3transitionsof[M-H]-(m/z:321)(321→152,321→194and321→257)Q1peakwidth

0.7DainSRMor0.2DainH-SRMQ3peakwidth0.7DaCollisionPressure:Arat1.3mTorrOHOHNHHHOClClO2NQ1peakwidthandH-

SRMexperimentEnablingtheH-SRMexperimentHighlySelectiveSelectedReactionMonitoring(H-SRM)Reduces“isoba

ric”chemicalnoiseIncreasesconfidenceofanalysis&improvedLOQQ1peakwidth0.7DainSRMor0.2DainH-SRMQ3peakwidth0.7DaO

HOHNHHOClClO2NONHHNOClClOHONHHHOClClO2NOHO2NOHCO2NOHHm/z321m/z257m/z321m/z194m/z152CAPSRMResult:CAPStandardQ1peakwidth=0.7DaRT: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)02040608010002040608010002040608

0100RelativeAbundance020406080100RT:2.83AA:60868SN:15803.843.254.652.341.030.802.473.561.530.324.523.113.431.731.880.172.064.872.644

.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:2.8

3AA:13035SN:1644RT:2.83AA:24218SN:6393.843.252.341.030.802.474.593.564.761.530.323.113.431.734.431.880.172.062.644.174.311.230.5

41.402.20NL:1.82E4TICF:MSICIS1221C03NL:7.07E3BasePeakm/z=151.50-152.50F:MSICIS1221C03NL:4.48E3BasePeak

m/z=193.50-194.50F:MSICIS1221C03NL:6.77E3BasePeakm/z=256.50-257.50F:MSICIS1221C03TIC321->152321->194321->257CAPPeakAreaCounts=2.4E

4CAPSRMResult:KidneyBlankRT: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)02040608010002040

6080100020406080100RelativeAbundance0204060801001.281.481.751.892.052.612.231.032.832.462.953.073.223.783.480.694.603.624.324.060.3

64.870.184.454.720.512.772.052.231.851.641.522.421.772.572.953.253.351.313.544.321.034.163.974.870.420.930.224.723.824.463.690.811.1

80.662.152.682.991.651.852.293.212.831.372.392.033.524.504.013.673.451.124.610.194.924.324.200.940.420.820.691.281.481.751.892.612.052.231.032.462.83

3.073.293.783.490.694.603.624.060.364.374.214.830.180.51NL:5.30E4TICF:MS1221D05NL:1.79E3BasePeakm/z=151

.50-152.50F:MS1221D05NL:4.69E2BasePeakm/z=193.50-194.50F:MS1221D05NL:5.27E4BasePeakm/z=256.50-257.50F:MS1221D05TIC321->152321->194321->257C

APSRMResult:KidneySpiked(0.5ng/g)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)020406080100020406080100020406080100RelativeAbundance0204060801001.292.061.482.881.842.262.421.082.762.

623.033.343.483.973.624.943.784.814.390.580.130.464.240.280.774.104.66RT:2.88AA:13715SN:30RMS2.231.572.111.452.451.821.28

3.342.593.483.933.191.124.163.710.694.390.434.710.190.870.554.864.54RT:2.88MA:6787SN:17RMS2.511.882.661.661.081.261.9

72.261.473.820.950.724.123.033.204.673.654.403.374.854.543.980.550.330.134.26RT:2.87MA:14653SN:INF1.292.061.481.842.291.002.422.613.033.253.393.973.

624.943.784.814.390.580.130.464.240.280.774.104.66NL:4.68E4TICF:MS1221D08NL:3.47E3BasePeakm/z=151.50-152

.50F:MSICIS1221D08NL:2.26E3BasePeakm/z=193.50-194.50F:MS1221D08NL:4.63E4BasePeakm/z=256.50-257.50F:MS1221D08TIC321->152321->

194321->257CAPNotaccurateforconfirmationCAPdetectedCAPH-SRMResult:CAPStandardQ1peakwidth=0.2DaRT:0.00-5.000.00.20.40.60.81.01.21.41.61.82.02.22.4

2.62.83.03.23.43.63.84.04.24.44.64.8Time(min)020406080100020406080100020406080100RelativeAbundance020406080100RT:2.89AA:16306SN:1762RMS

1.661.780.221.153.864.324.893.462.031.010.551.512.302.614.593.311.320.773.083.680.363.994.202.732.444.724.442.15RT

:2.89AA:7313SN:24498RMS3.423.083.854.384.831.073.980.151.331.532.061.763.673.301.932.560.362.200.492.694.1

20.690.884.592.36RT:2.91AA:1841SN:273RMSRT:2.89AA:7129SN:768RMS1.661.780.221.154.323.863.461.012.030.552.301.512.614.593.311.324.870.773.680.364.2

02.444.003.074.724.46NL:5.46E3TICF:MSICIS1221G11NL:2.39E3BasePeakm/z=151.50-152.50F:MSICIS1221G11NL:7.50E2BasePeakm/z=193.50-194.50F:MSICIS1221G11NL

:2.46E3BasePeakm/z=256.50-257.50F:MSICIS1221G11TIC321->152321->194321->257PeakAreaCounts=7.3E3CAPH-SRMResult:KidneyBlankRT: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)020406080100020406080100020406080100RelativeAbundance02

04060801001.301.782.051.952.591.471.012.412.201.672.853.220.290.520.733.504.643.864.320.863.330.114.114.894.774.443.691.521.623

.111.871.432.264.641.774.320.953.332.832.550.751.214.843.560.454.150.580.193.854.544.013.731.133.862.73

2.922.580.222.461.621.502.060.991.292.351.724.373.371.420.670.802.224.690.481.850.144.093.103.244.943.56

3.731.301.782.051.952.591.471.012.412.202.853.220.290.520.733.503.110.860.114.114.624.894.233.863.69

4.41NL:2.08E3TICF:MS1221G04NL:2.14E2BasePeakm/z=151.50-152.50F:MS1221G04NL:2.70E1BasePeakm/z=193.50-194.50F:MS1221G04NL:2.06E3BasePeakm/z

=256.50-257.50F:MS1221G04TIC321->152321->194321->257NoCAPdetectedCAPH-SRMResult:KidneySpiked(0.5ng/g)RT:0.00-5.000.00.20.40.60.81.01.21.41.6

1.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.8Time(min)020406080100020406080100020406080100RelativeAbundance020406080100RT:2.86MA:779

9SN: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:274RMS2.061.461.651.921.292.241.112.641.773.293.964.492.404.934.700.983.783.093.554.130.530.800.300.144.330.67RT:2.85AA:1107SN

:240RMS1.564.891.661.382.362.191.051.172.042.604.430.163.333.493.103.992.724.133.861.863.640.794.260.534.780.390

.674.60RT:2.86MA:3554SN:1NL:2.45E3TICF:MS1221G07NL:8.97E2BasePeakm/z=151.50-152.50F:MSICIS1221G07NL:3.82E2BasePeakm/z=19

3.50-194.50F:MSICIS1221G07NL:2.39E3BasePeakm/z=256.50-257.50F:MS1221G07TIC321->152321->194321->257CAP2.3.2黄杨宁生物碱HPLC-MS联用鉴定黄杨科植物小叶黄杨BuxusmicrophllaS

ieb.et.Zucc.var.sinicaRehd.etWils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色谱图色谱条件•色谱柱：Lichro

spherSiO2(250mm×4.6mm,5µm)•流动相：四氢呋喃-甲醇-乙腈-氨水(32:50:13:3)•流速：1mL·min-1•柱温：30℃•ELSD参数：漂移管温度70℃雾化气体（N2）流速：1.5L·min-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%186.853.578.090.790.9213.37287.083.848.540.800.9814.15385.833.468.8

20.810.9514.03485.703.548.760.870.9314.10585.053.528.640.740.8513.75684.843.749.030.790.9714.53Mean85.893.6

18.650.800.9313.99RSD%1.073.653.384.624.632.8环维黄杨星D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35

0℃碰撞气氩气压力1.5mTorr•色谱条件色谱柱：LichrospherSiO2(250mm×4.6mm,5µm)流动相：四氢呋喃-甲醇-乙腈-氨水(32:50:13:3)流速：1mL·min-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NOCH3CH3NCH3CH3HOCH3H

ONHNHOCH3CyclobuxomicreineKCyclobuxosuffrineKBuxenoneMCyclobuxoviridineB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NNHCH3CH2OHCH3CH3OHNONHCH3CH2OHCH3C

H3NOHNOCH3CH3CH3NCH3CH2OHCH3OHNHCH3CyclomicrophyllineBBuxazidineBCyclobuxoxazineCCyclomicrophyllineC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NNCH3CH3CH3CH3NNHCH3CH3OHCH3NNHCH3CH3OHCH3NHNCH3CH2OHCH3CH3CycloprotobuxineACyclokreanineBCyclovirobuxeine

B16-deoxybuxidienineC峰4母离子质荷比峰4二级质谱图CH3CH3NHCH3CH3OHNHCH3HCH3HCH3CH3环常绿黄杨碱C[M+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NCH3CH3CH3NHNH2CH3

OHNCH3NCH3CH3CH3NCH3CH3CH3NCH3CH2NHOHCycloprotobuxineCBuxaminolEBuxocyclamineACyclobuxineB峰6母离子质荷比峰6二级质谱图NH

CH3CH3OHNHCH3HCH3HCH3CH2环黄杨碱D[M+H]+=387峰7母离子质荷比峰7二级质谱图CH3CH3NHCH3CH3OHNHCH3HCH3HCH3环维黄杨星D[M+H]+=403峰8母离子质荷比[M+H]+=375357.15峰8二级质谱图峰9二级质谱图3

71.17CH3OHNH2CH3HCH3HCH3CH3NH2＋－H2OCH3NH2CH3HCH3HCH3CH3NH2＋CH3OHHCH3HCH3CH3NH2＋CH3HCH3HCH3CH3NH2＋CH3HCH3HCH3CH3＋NH2CH3－－H2O

NH3－m/z=375m/z=357m/z=344m/z=326m/z=309357.15NHCH3CH3OHNHCH3HCH3HCH3CH2峰9母离子质荷比[M+H]+=389NHCH3CH3OHNHCH3HC

H3HCH3CH3峰9二级质谱图371.17NHCH3CH3OHNH2CH3HCH3HCH3CH3＋－H2ONHCH3NH2CH3HCH3HCH3CH3＋NH2CH3－NHCH3OHHCH3HCH3CH3＋－H2ONHCH3CH3HCH3HCH3CH

3＋NH2CH3－CH3HCH3HCH3CH3＋m/z=389m/z=371m/z=358m/z=340m/z=309371.17峰位号tR(min)[M+H]+(m/z)特征碎片离子(m/z)可能生物碱名称13.9237

0339，325，283，135，70，58CyclobuxomicreineK,CyclobuxosuffrineK,BuxenoneM,CyclobuxoviridineB24.03431413，382，323，86，70，58BuxazidineB,Cyclomicro

phyllineB,CyclobuxoxazineC,CyclomicrophyllineC35.35415384，84，58CycloprotobuxineA,CyclokreanineB,CyclovirobuxeineB,16-deoxybux

idienineC45.92417399，386，368，84，58CylcyclovirobuxineC56.11401370，352，326，171，58CycloprotobuxineC,BuxaminolE,BuxocyclamineA,CyclobuxineB6

7.03387369，356，338，171，58CyclobuxineD77.63403385，372，354，70，58CyclovirobuxineD88.28375357，344，326，309，58未有相关文献报道99.7738

9371，358，340，173，70，58可能为CyclobuxineD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(RizatriptanBenzoate)MW:391.4

7分子式：C15H19O5·C7H6O25-HT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药理作用❖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；❖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；❖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；❖刺激脑干5-HT1B或5-HT1D受体，抑制三叉神经核兴奋；❖减少颈动脉血流；❖透过血脑屏障，增加脑血流量。实验内容❖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❖苯甲酸利扎曲普坦分散片和胶囊进行生物等效性试验❖苯甲酸利扎曲普坦片体内药代动力学研究单剂量(5,10,15mg)多次给药(10mg)稳态(10mg)LC-MS/MS测定方法建立❖测定方法选择❖质谱条件优化❖色谱条件选择色谱柱选择缓冲盐选择❖血浆处理方法液液萃取法蛋白沉

淀法❖内标选择LC-MS/MSm/z270m/z158PhenomenxPFP1%冰醋酸,0.2%醋酸铵蛋白沉淀法盐酸曲马多色谱条件流动相A：醋酸盐缓冲液(1%冰醋酸，2%醋酸铵;pH3.5)流动相B：甲醇

(0.1%甲酸)梯度条件过程：0min(B50%)→1.0min(B95%)→4.5min(B95%)→4.6min(B50%)→6.5min(B50%)010203040506070809010001234567T(min)MeOH(%)

空白溶剂色谱图预处理的空白血浆色谱图RT:0.00-6.500246Time(min)020406080100020406080100NL:1.00E5TICF:+csid=-12.00SRMms2263.90@-

20.00[57.99-58.00]MSwashNL:1.00E3TICF:+csid=-12.00SRMms2269.90@-20.00[158.10]MSwashRT:0.00-6.500246Time(min)020406080100020406080100Relativ

eAbundanceNL:1.00E5TICF:+csid=-12.00SRMms2263.90@-20.00[57.99-58.00]MSM-Cline-4-01NL:1.00E3TICF:+csid=-12.00SRMms2269.90@-20.00[15

8.10]MSM-Cline-4-01质谱条件离子检测方式：ESI+SRM检测对象：利扎曲普坦m/z269.9→158.1曲马多m/z263.9→58.0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：1.3mTorr碰撞能量：20e

V质谱条件优化LZQPT#2385RT:20.83AV:1NL:1.95E5T:+csid=-8.00Q3MS[170.00-350.00]180200220240260280300320340m/z0102

030405060708090100270.14187.02274.25340.23241.02318.24286.14228.01301.03346.26247.05182.08222.04262.24312.25205.97288.09328.17利扎

曲普坦LC-MS质谱扫描图（m/z=270）LZQPT#2994RT:26.34AV:1NL:3.60E5T:+csid=-8.00Fullms2270.00@-25.00[50.00-350.00]50100150200250300350m/z010203040506070809010

0158.0358.10201.08155.92172.00225.03129.9490.86270.5159.24332.51314.94利扎曲普坦LC-MS/MS质谱扫描图（m/z=158）NNNNHN6844NHm/z270m/z1

58利扎曲普坦质谱裂解图m/z270m/z158（碰撞能量：20ev）色谱条件选择色谱柱Intersil-ODSC18Lichrospher-C18Zorbak-ODSC18Lichrospher-CNPhenomenxCurosil-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）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，拖尾得到一定程度的改善。0.

1%HCOOH0.1%HAC0.2%HAC0.5%HAC1.0%HAC1%HAC水相pH值为3.5，样品保留时间合适，峰形良好。血浆处理方法碱化液样品体积(µl)回收率(%)乙酸乙酯1MNaOH10071.8空白血浆有明显干扰乙醚1MNaOH10070.9空白血浆略

有干扰氯仿1MNaOH10045.9无干扰二氯甲烷1MNaOH10058.4空白血浆干扰，特丁基醚1MNaOH10089.9空白血浆无明显干扰特丁基醚0.1MNaOH5076.8无干扰特丁基醚0.1MNaOH10070.8空白血浆有干扰特丁基醚0.1MNaOH20075无干

扰特丁基醚1MNaOH5088.2无干扰特丁基醚1MNaOH20092.4无干扰特丁基醚浓氨水5088.5无干扰特丁基醚浓氨水10083.8无干扰特丁基醚浓氨水20081.7无干扰提取溶剂碱化液种类结论苯甲酸利

扎曲普坦血浆提取条件试验内标选择OHNOHNN佐米曲普坦(Zolmitriptan)MW：287分子式：C16H21N3O2HONCH3H3COCH3.HCl盐酸曲马多(Tramadolhydrochloric)MW：299.8分子式：

C16H25NO2tmd#176RT:3.03AV:1SB:810.55-1.93NL:2.03E6T:+csid=-10.00Q3MS[50.00-350.00]50100150200250300350m/z0102030405060708090100264.10157.

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#3619-4202RT:14.32-16.85AV:565NL

:9.20E5T:+csid=-12.00Fullms2263.90@-25.00[30.00-350.00]50100150200250300350m/z010203040506070809010057.

95218.90263.8655.98120.96159.02203.3099.1766.93341.37316.23301.11曲马多LC-MS/MS质谱扫描图（m/z=58）OHNH3CH3COCH3206NH3CH3Cm/z264m/z58CH3曲马多质谱裂解

图m/z264m/z58单次给药受试者单次口服苯甲酸利扎曲普坦片后，苯甲酸利扎曲普坦的Cmax和AUC与服药剂量成正比关系。y=3.3132x-0.3037R2=0.9328010203040506005101520dose(mg)Cmax

y=12.508x-14.841R2=0.987505010015020005101520dose(mg)AUCCmax－DoseAUC－Dose数据分析0510152025303540455002468101214时

间(h)浓度(ng/ml)5mg10mg15mg受试者单剂量口服低中高剂量后的平均血药浓度-时间曲线02468101214161802468101214时间(h)平均累计排泄量(%)5mg10mg15

mg受试者单剂量口服低中高剂量后的平均累积排泄量-时间曲线00.511.5201234567时间(d)浓度(ng/ml)受试者多次服药第3～6天时平均谷时血药浓度-时间曲线051015202530024681012

14时间(h)浓度(ng/ml)受试者多次口服达稳态后的平均药时曲线2.4其他质谱技术与特点创新意识不断探索勇于实践谢谢大家！