Improved Instrument Robustness via a Hot Source ...

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... liquid chromatography tandem mass spectrometry (LC-MS/MS) as a gold standard ... Frank Kero2, Josh Ye2, Jason Weisenseel2, Craig Young2, Jamie Foss2.
“Improved Instrument Robustness via a Hot Source Induced Desolvation (HSID) Interface for Tandem Mass Spectrometry Instrumentation” Alessandra Bruno1, Chris Mulligan1, Tom Jacobs2, Frank Kero2, Josh Ye2, Jason Weisenseel2, Craig Young2, Jamie Foss2 1. Illinois State University, Department of Chemistry, Campus Box 4160, Normal, IL 61790-4160 2. PerkinElmer Environmental Health, 2651 Warrenville Road, Ste. 100, Downers Grove, IL 60515

HSID principles of operation

Introduction The emergence of liquid chromatography tandem mass spectrometry (LC-MS/MS) as a gold standard analytical platform for quantitative method development in high throughput toxicology, environmental surveillance and food safety laboratories has been well documented. Recent trends in practical considerations for improvements towards laboratory implementation focus on reduced downtime to facilitate testing methods for large sample populations. This poster will report on related strategies with a special focus on a dual spray ionization apparatus equipped with a heated coaxial flow ion source. The result yields a path for ion introduction into the orifice of the mass spectrometer using multi-orthogonal channels and laminar flow sampling. The advantages for this platform include high sensitivity due to an inherent reduction in chemical background (i.e. S/N, reduced N). Instrument ruggedness and stability are also improved due to orthogonal sampling and laminar flow. The laminar flow phenomenon is achieved by a combination of the influences of gas flow dynamics and electric fields. Ions are orthogonally extracted at atmospheric pressure and focused through a series of channels and turns entrained in a hot laminar flow of gas (different than traditional mass spectrometry instrumentation). Efficient desolvation is accomplished as a result of sequential energy transfer events. The flow of gas evolves through multiple transitions beginning with supersonic transitioning to shock cascading to turbulent and decreasing to laminar flow. The reduction in the speed of ion transmission is important to maintaining the sensitivity advantages of this interface.

Robustness study: No prep- Pesticide Residue Analysis in Wine

In comparison with ion funnel sampling Traditional sampling

Solid Phase Extraction Post-mortem Hemolyzed Blood

Graph of peak area vs. injection number for Pyriproxyfen (blue), Benthiavalicarb-isopropyl(green), and Dimethenamid(red) for Pinot Grigio (a) and Carbernet (b).

4

8 Ring guide/ion funnel

Po=760 T

Ion guide

Zone of silence

5

P= Torr

2 1

Nozzle

PerkinElmer Qsight 220 Laminar Flow Tandem Mass Spectrometer

Benzoylecgonine Cocaine EDDP Methadone Nordiazepam Alprazolam Temazepam Diazepam

Zone of silence Zone of silence Zone of silence

Capillary

• • • • •

1 2 3 4 5 6 7 8

6 3

7

Clustering High chemical background Requires frequent cleaning Large difference from one system to another Sever signal fluctuation

HSID operates like mushrooms dancing on hot oil, never touch bottom of pan.

Fast and robust screening of 210 pesticides in five non-organic berries by LC-MS/MS with simple QuEChERS preparation

Ion Exchange SPE for Metanephrine / Normetanephrine Plasma (n=32) interlab comparison with Mayo Clinic Correlation plots

Flow-Based a Core Technology in Tandem MS Systems

1-

Formation and propagation of the free jet (1000 m/s)

2- Complete destruction of free jet expansion

HSID body 0-300 0C

 Flow-based mass spectrometer, the latest innovation in MS

3- Creation of turbulent Energy transfer from background gas to solvated ions

 Coaxial flow ion Source, proprietary technology

4- Formation of fast laminar flow (>300 m/s) Preventing ions to scatter to the walls

 Self-cleaning interface (HSID), patented technology

5- Creation of second turbulent More energy transfer from background gas to solvated ions

 Laminar flow ion guides, patented technology

6- Formation of med-fast laminar flow (100 m/s) Preventing ions to scatter to the walls

 Mass filters, high resolution, proprietary technology

7- Further slowing down laminar flow ( >50 m/s)

 Most efficient collision cell, low crosstalk, patented technology

8- Forming a gradient flow source for MP0 ion guide

MP0 Ion guide

Liquid Extraction of Veterinary drug residues in adulterated pig feed (authentic samples)

 Unifield detector, simultaneous detection of positive and negative ions patented technology

Unsuspected Exposure to Drugs of Abuse in Young Children Presenting for Emergency Care (hydrolyzed urine)

Recent Published Applications References Coaxial Flow-Based ESI A New Approach to ESI Efficiency

Mixing region

Sample spray plume

Hot gas 0-500 oC

1 µL injection

:

Meglioli M, Kero F, Ye J, Young C, Reddy S “”No dilute” just shoot LC-ESI-MS/MS : feasibility and robustness of a maintenance-free source for applications in low-level pesticide residue analysis”The Proceedings of the 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX, June 2016 Ye J, Kero F, Young C, Reddy S”Fast and robust 210 multi-residue pesticide screening of five washed and unwashed non-organic berries by LC-MS/MS with simple QuEChERS preparation” The Proceedings of the 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX, June 2016 Kong J, Kero F, Ye J, Cousins L, Young C, Reddy S “Extending the linear dynamic range for measurements targeting veterinary drug residues in animal feed by UPLC-laminar flow HSID-MS/MS”The Proceedings of the 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX, June 2016 Botch S, Le Blanc R, Ye J, Kero F, Young C, Schmidt C “The Simultaneous Detection of a Panel of Drugs of Abuse in Post-mortem Hemolyzed Blood Samples (n=40) by LC-ESI-laminar Flow MS/MS” HPLC 2016 44th International Symposium on High Performance Liquid Phase Separations and Related Techniques, San Francisco, CA June 2016 F.A. Kero , J. Ye , T. Enzweiler , V. Vandell , E. Gairloch , E. Majdi , H. Qiao , L. Cousins “A reduced workflow SPE- LC-ESI-MS/MS method to distinguish healthy from elevated concentrations of metanephrine and normetanephrine in patient plasma samples” Clinical Chemistry, Vol. 60, No. 10, Supplement, 2014, A-397, pages S116-S117 Qin F, Ye J, Neuman G, Kero F, Young C, Reddy S, Chai Y, Colantonio D “Unsuspected Exposure to Drugs of Abuse in Young Children Presenting for Emergency Care” The Proceedings of the 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX, June 2016

De-identified patient sample Urine specimens were hydrolyzed using beta-glucuronidase, extracted with methanol and then centrifuged

Sulfamethazine – 10 grams of sample /0.1L Samples were extracted with a 1:1 Methanol:Water solution and put on a rotary shaker for 30 min.

Tylosin – 25 grams of sample / 0.1L Samples were extracted with a 1:1 Methanol:Buffer solution and put on a rotary shaker for 30 min. Buffer was composed of 16.73 g K2HPO4 and 0.52 g KH2PO4 (aq) diluted to 1 L.

Sampling region

Nebulizing gas

Poster presentation for Chicago Mass Spec day July 2016: for more information contact [email protected]

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