Changing the Game in LC-MS/MS New Tools for Unprecedented Performance in Residue Analysis Dr. Thomas Glauner EMEA LC/MS Food Segment Scientist Agilent Technologies Waldbronn
The New 6490 Triple Quadrupole LC/MS 6490 Technology Review ifunnel Curved Collision Cell Electronics Sensitivity Enhanced Resolution Data Review Sensitivity Data Pesticides and PPCPs in Water Software tools for QQQ applications 2
6490 The New High Sensitivity Triple Quadrupole Ionization and Ion Transfer Technology Agilent Jet Stream Ion Generation Hexabore capillary Dual ion funnel (DIF) technology Two stages for ion focusing and gas removal Improvements for wide m/z range transmission Low capacitance Collision Cell Hexapole field axial focusing curved collision cell Tapered cell structure for increased ion acceptance at entrance Reduced noise Improved Quad Drive Electronics Improved Quad DC frequency response Higher RF power capability Quad drive frequency increased to 1.4 MHz 3
Hexabore Atmospheric Sampling. SIX bores HALF as long 6 Bore Capillary Six bores, Half the restriction means 6 times the amount of atmospheric gas sampled AND 5 10X the number of ions sampled over wide mass range. But how do we handle all the extra gas molecules? Compare: Standard Capillary is 180mm 4
Agilent s Two Stage Ion Funnel Can Handle the Gas Load High Pressure Stage 1 Low Pressure Stage 2 Existing RF Ion Guide Stage 1 8-12 Torr Stage 2 1-3 Torr Stage 1 offset breaks up the high pressure gas exiting the Hexabore Capillary 5
How Does an Ion Funnel Work? RF Voltage focuses the ions to the center. RF Drive Unfocused Ions and Gas Enter Focused Ions Out DC Voltage accelerates the ions to the exit. DC Drive
Triple Quadrupole Instrument Configurations 6460 LC/MS (Skimmer Configuration) Cap RF Ion Q1 Coll Q3 Guide Cell Ion Detector Ion Detector Q3 6490 LC/MS (ifunnel Configuration) Curved Collision cell HB Cap Dual Ion RF ion Q1 Funnels guide
Improved Ion Sampling Efficiencies Agilent Jet Stream positive ion Agilent Jet Stream negative ion 7x 7x 7x 5x 5x 6490 14x 11x 10x 7x 10x 118 622 922 6460 322 1222 302 1034 113 200 400 600 800 1000 1200 1400 m/z 200 400 600 800 1000 1200 1400 m/z
6490 with ifunnel vs 6460 in Positive Ion Mode 1 pg Reserpine (7X) 1 pg Alprazolam (6X) x10 3 6490 x10 3 6490 3 2 1 6460 6460 0 0.1 0.2 0.3 0.4 0.5 0.6 Time (min) 0 0.2 0.4 0.6 0.8 1.0 1.2 Time (min) 9
6490 with ifunnel vs 6460 in Negative Ion Mode 1 pg Chloramphenicol (8X) 1 pg Acid red 4 (9X) x10 3 2 6490 x10 3 6490 1 0.8 0.6 1 0.4 6460 0.2 6460 0 0.5 1 1.5 2 Time (min) 0 0.2 0.4 0.6 0.8 1 Time (min) 10
New 6490 Triple installation Spec: S/N > 10,000:1 so the 6490 should be able to detect 1 fg? 1 pg reserpine on-column S/N > 22,605:1
The 6490 - Attogram Sensitivity for Reserpine 1 fg of reserpine injected on-column S/N is as predicted Time [min]
Trace Analysis of Pharmaceuticals: Overall Goals Instrumentation Evaluation 6490 for Direct Aqueous Injection Wastewater Analysis Drinking Water Analysis and the 1 ppt Detection Barrier Data generated by: E. Michael Thurman and Imma Ferrer Dept of Civil, Environmental, and Architectural Engineering Center for Environmental Mass Spectrometry (CEMS), University of Colorado, Boulder, CO, USA
Albuterol: 1 ng/l Direct Injection in Water 40 fg on column LOD 1 ng/l Albuterol: Bronchodilator OH HO H N C(CH 3 ) 3 HO 5 ng/l Albuterol
Dehydronifedipine: 40 fg on column from Water Sample LOD 1 ng/l Dehydronifedipine: Anti-anginal H 3C N CH 3 H 3CO OCH 3 O O NO 2 5 ng/l
High sensitivity achieved with combination of Jet Stream and ifunnel Technology Carbamazepine ng/l QqQ 6410 QqQ 6460 Jet Stream QqQ 6490 Ion Funnel Acetaminophen 0.5-1 ppb 3 times 20 times Caffeine 0.5-1 ppb 2 times 10 times Carbamazepine 0.5-1 ppb 3 times 20 times Sulfadimethoxine 0.5-1 ppb 3 times 20 times
Limits of Detection for 6490 with Direct Aqueous Injection of 40 µl water sample Compound On Column (fg) LOD in Water sample Compound On Column (fg) LOD in Water sample Acetaminophen 1000 25 ppt Albuterol 40 1 ppt Atenolol 200 5 ppt Caffeine 2000 50 ppt Carbamazepine 40 1 ppt Cotinine 400 10 ppt Dehydronifedipine 40 1 ppt Diltiazem 200 5 ppt Diphenhydramine 400 10 ppt Metoprolol 200 5 ppt Sulfadimethoxine 400 10 ppt Sulfathiazole 1000 25 ppt Trimethoprim 2000 50 ppt Diclofenac (Neg Ion) 4000 100 ppt Gemfibrosil 2000 50 ppt Naproxen 20,000 500 ppt Triclocarban 400 10 ppt Triclosan 2000 50 ppt
Trace Analysis in Water using the 6490 Poster at ASMS 2010 18
6490 Pesticide Analysis Calibration Plots Example Calibration Plots, 1-100 ppt (6 levels, 3 replicates.) Mexacarbate (carbamate insecticide) Fenuron (phenylurea herbicide) 1 ppt SNR 326 R 2 = 0.9994 1 ppt SNR 50 R 2 = 0.9990 Secbumeton (triazine herbicide) Metolachlor (chloroacetanilide herbicide) 1 ppt SNR 32 R 2 = 0.9977 R 2 = 0.9988 1 ppt SNR 225 Low PPT to sub-ppt level detection of pesticides in water by on-line SPE-LCMS/MS 19
Ultra Trace Levels of Pesticides in Potable Water 11 Triazine herbicides analyzed at 50 parts per quadrillion level in water Atraton s/n: 819 s/n is calculated based upon peak height and 5*RMS noise 6490 Triple Quad with online enrichment Simazine s/n: 18 Ametryn s/n: 56 Simetryn s/n: 9 Propazine s/n: 15 Secbumeton s/n: 51 Terbuthylazine s/n: 33 Prometon s/n: 40 Prometryn s/n: 54 Atrazine s/n: 28 Terbutryn s/n: 59 20
Fast method setup using LC/MS Application Kits Add Application Kit to your LCMS Instrument: - pre-defined methods - Accurate mass databases and libraries for TOF and QTOF - Dynamic MRM databases for QQQ Use one of the following Application Kits: G6854AA -- Pesticide Personal Compound Database kit G3876AA PCDL Database & Library Forensics/Toxicology kit G1733AA -- Pesticides Dynamic MRM Database Kit G1734AA -- Forensic/Tox Dynamic MRM Database Kit 21
Fast review with new Compounds at a Glance Free configurable peak review window allows fast reviewing up to 100 compounds and samples at one time New MH Quant B.04.00 - organize by samples or compounds - overlay of qualifiers or ISTDs - normalize axis - flag for outliers 22
New 6490 LC Triple with ifunnel Technology Conclusion 1290 Infinity LC/6490 Triple : Clearly Better Together High Pressure High Speed High Sensitivity