不同離子源的適用范圍以及API串聯(lián)四級桿質(zhì)譜特性

1、AB SCIEX Triple Quad Quantitative Applications Biosystems， Introduction of general ion source and unique features ofAPI instruments不同離子源的適用范圍以及API串聯(lián)四級桿質(zhì)譜的特性Improved fast LC support 更好的超高速液相支持系統(tǒng)Qtrap functions and 3for quantitationQTRAP功能以及MRM 在定量中的應(yīng)用321CFR compliant software tools and consistentperf

2、ormance for validated studies符合21CFR法規(guī)的軟件以及穩(wěn)定儀器性能更適用于認(rèn)證的實(shí)驗(yàn)2October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND1不同離子源的適用范圍以及串聯(lián)四級桿質(zhì)譜的特性3October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND4October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint

3、 OwnersABOVE & BEYOND2Electrospray (ESI)電噴霧離子化ionizes compounds in theliquid phase.Atmospheric Pressure Chemical Ionization (APCI)大氣壓化ionizes compounds in the gas phase using a學(xué)離子化corona discharge.Atmospheric Pressure Photo大氣壓光離子化 -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. 液滴蒸發(fā)，液滴里的場強(qiáng)增加3. 離子從液滴中迸發(fā)出來，在接口處聚焦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. 電荷在非極性化合物間傳遞 上面所示)2. 極性化合物溶劑傳遞8October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND4適合非離子非極性熱穩(wěn)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 & 適合大范圍的化合物-小和極性 不穩(wěn)定性和揮發(fā)性不是問題 的子式 極性化合物離子化 寬動態(tài)范圍(4 -5數(shù)量級） 質(zhì)量敏感（依賴流） 高緩沖濃度 大子量（多電荷）化合物高靈敏度 化合物穩(wěn)定 (高 130-150C) 揮發(fā)性 需要摻雜劑(APPI)11October, 20082008 Applied BiosystemsInc.and MDS Inc.

7、 Joint OwnersABOVE & BEYOND (針對 API 3200, API 4000,& API 5000系統(tǒng)) 對稱加熱裝置，最高溫度可 含2個離子源 : ESI & APCI12October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND6 RecirculationEntrainment 對稱的 高瓦特密度加以持集中噴，稱為夾帶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流速被細(xì)液滴噴霧在液滴陶瓷壁之間形成蒸汽最佳導(dǎo)形成液滴解吸附熱梯度化合物的降解并且具自我清潔能力得到的更，顯提高S/N15October, 20082008

9、Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND8HighwayLINAC離子，象交通中的車子，如果被分開很容易分辨。交通堵塞時，很難辨一個車子和子有LINAC ，質(zhì)譜很難辨一個質(zhì)量的結(jié)束另一個質(zhì)量數(shù)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統(tǒng)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功能在定量中的應(yīng)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法規(guī)的軟件以及穩(wěn)定儀器性能更適用于認(rèn)證的實(shí)驗(yàn)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系統(tǒng)45October, 20082008 Applied BiosystemsInc.and MDS Inc. Joint OwnersABOVE & BEYOND Settings查46October, 20082008 Applie