不同离子源的适用范围以及API串联四级杆质谱特性

1、AB SCIEX Triple Quad Quantitative Applications Biosystems， Introduction of general ion source and unique features ofAPI instruments不同离子源的适用范围以及API串联四级杆质谱的特性Improved fast LC support 更好的超高速液相支持系统Qtrap functions and 3for quantitationQTRAP功能以及MRM 在定量中的应用321CFR compliant software tools and consistentperf

2、ormance for validated studies符合21CFR法规的软件以及稳定仪器性能更适用于认证的实验2October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND1不同离子源的适用范围以及串联四级杆质谱的特性3October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND4October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint

3、 OwnersABOVE & BEYOND2Electrospray (ESI)电喷雾离子化ionizes compounds in theliquid phase.Atmospheric Pressure Chemical Ionization (APCI)大气压化ionizes compounds in the gas phase using a学离子化corona discharge.Atmospheric Pressure Photo大气压光离子化 -Ionization(APPI) ionizes compounds in the gas phase using UVradiatio

4、n and a dopant to induce ionization.5October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND Vacuum1.2. 2. 液滴蒸发，液滴里的场强增加3. 离子从液滴中迸发出来，在接口处聚焦6October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND3Atmospheric PressureVacuum1.2.3. 7October, 20082008 App

5、lied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND1. 电荷在非极性化合物间传递 上面所示)2. 极性化合物溶剂传递8October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND4适合非离子非极性热稳定化合物TM9October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND Q1Q397CXP4TIS33133110920Q1Q397C

6、XP4APCIAPPI33133110920Q1Q3973313311092010October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND5 & 适合大范围的化合物-小和极性 不稳定性和挥发性不是问题 的子式 极性化合物离子化 宽动态范围(4 -5数量级） 质量敏感（依赖流） 高缓冲浓度 大子量（多电荷）化合物高灵敏度 化合物稳定 (高 130-150C) 挥发性 需要掺杂剂(APPI)11October, 20082008 Applied BiosystemsInc.and MDS Inc.

7、 Joint OwnersABOVE & BEYOND (针对 API 3200, API 4000,& API 5000系统) 对称加热装置，最高温度可 含2个离子源 : ESI & APCI12October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND6 RecirculationEntrainment 对称的 高瓦特密度加以持集中喷，称为夹带13October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE &

8、BEYOND ,DeclusteringPotential (DP)2-rroQ0,Curtain gasTm EntranceAtmosphericPressure8Potential (EP)-6Pressures due to Differential Pumping14October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND7LC流速被细液滴喷雾在液滴陶瓷壁之间形成蒸汽最佳导形成液滴解吸附热梯度化合物的降解并且具自我清洁能力得到的更，显提高S/N15October, 20082008

9、Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND8HighwayLINAC离子，象交通中的车子，如果被分开很容易分辨。交通堵塞时，很难辨一个车子和子有LINAC ，质谱很难辨一个质量的结束另一个质量数的始。17October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYONDwith LINAC Collision CellCross-talk for amphetamineInjection of selegiline (IS)

10、 to determine the level of cross-talkin the amphetamine (none present) MRM transition in non-Linac Q218October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND9Sensitivity of API 4000 source over extended flow range4.0e43.5e43.0e42.5e42.0e41.5e41.0e45000.00.00.0 0.5 1.0 1.5 2.

11、0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0Time, min19October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND 20October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND10更好的超高速液相支持系统21October, 20082008 Applied BiosystemsInc.and MDS Inc. Jo

12、int OwnersABOVE & BEYOND Increased responseConventional LCIncreased throughputBetter resolution Faster cycle times!Maintain response athigh LC flow rates22October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND11 Longer dwell times-poor precisionShort dwell times-better preci

13、sion3.11.11e53.12.93.03.23.32.93.03.23.323October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND Improving MRM Method Efficiency by Maximizing AnalyteUtilizationEach MRM monitored only across its expected elution time effective duty cycle for every peptide24October, 20082008

14、 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND12- - 25October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYONDXIC of +M RM (22 p airs): 152.0/11 0.0 amu Expected RT:0.4 ID: Aceta minophem from Sample 11 (Sample001 - sMRM - 1) of Quant 55 0.Max. 1.9e5 cp s.0.420

15、.20.40.60.81.01.21.41.61.82.0Time, min26October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND13CVs 4000 QTRAPSystem vs. 5500 QTRAPSystemand sMRM5500 QTRAPQ1Q31234SulfamerazineSulfamethizoleSulfamethazineSulfachloropyridazineSulfadimethoxinePhenacetin567891011121314151617181

16、9202122TestosteroneNifedipineAcetaminophem4-hydroxydiclofenac4-hydroxymephenytoin1-hydroxybufuralol1-hydroxymidazolam6-hydroxytestosteroneoxidized nifedipineNew Collision Cell and sMRMimprovesCVs27October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYONDNo Loss in S/N when usin

17、g Polarity Switching ,(+/-)Caffeine ,(+/-) Lidocaine+) Lidocaine ty,+) Chlorotoluron,(+/-) Chlorotoluron 28October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND14QTRAP功能在定量中的应用29October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND 1 with MRM_EPIIn

18、terference peakInterference peakInterference peak30October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND151 31October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND 3Many assays suffer from interferences What if MRM is not selective enough?3gives an

19、 extra level of selectivity With the added LIT sensitivity of the QTRAP 5500 system,quantitation using MRM is a perfect solution for many3problem assays32October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND16Fast and Selective MS/MS/MS Quantitation with 3nd generation of p

20、roduct ions scanned out33October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND10g/kg in Matrix (MRM: %CV5, accuracy 90-110% ) S/N = 922 S/N = 497 Int S/N = 8S/N = 147 34October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND17Max. 9148.8 cps.90008500

21、8000750070006500600055002D ChromatographyQTRAP5500 systemMRM3Inte50004500nsity, cps40003500300025002000150010005002.720.86117.10170.059.94103.78 4.12 4.445.56 5.96 6.84 7.617.76 8.439.6211.00 11.27 12.0111 120352345678913141516October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE &

22、BEYONDTime, min符合21CFR法规的软件以及稳定仪器性能更适用于认证的实验36October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND18ICH Guideline: Analytical Procedures and Method Validation37October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND%38October, 20082008 Applied Biosy

23、stemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND19Bromocriptine 5 fgOn ColumnAB SciexTriple Quad 5500 system MRMCV = 3% for39October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYONDLinearity and Precision for 17-OHP STD Curve in Solvent40October, 20082008 Applied BiosystemsInc

24、.and MDS Inc. Joint OwnersABOVE & BEYOND20 FDA(Food and DrugAdministration) CDER(Center for DrugEvaluation andresearch)Investigations)BioequivalenceInvestigationsBranch41October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND thinking a rights to alternative if satisfies Advi

25、sed (by auditors) Articles and Conference Presentations The views expressed in this article are those of the authors and do notreflect official policy at the FDA. No official endorsement by the FDA isintended or should be inferred.42October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersAB

26、OVE & BEYOND21 FDA Presentation: Actual Use Problems *Careful analysisof the AnalystResults Table *C.T. Vishwanathan, BSAT, September 200543October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND a A 44October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND22 System系统45October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND Settings查46October, 20082008 Applie