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AccuTOF DART Evaluation for Postmortem Toxicology Screening

This study evaluates the Jeol Ltd. AccuTOF DART system for postmortem toxicology screening, focusing on urine, blood, and tissue testing. Learn about the methodology, strengths, reference materials, analysis methods, and case examples.

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AccuTOF DART Evaluation for Postmortem Toxicology Screening

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  1. Evaluation AccuTOFDART for Postmortem Toxicology ScreeningPeter R. Stout RTI International is a trade name of Research Triangle Institute

  2. NIJ Project • Grant No. 2006-DN-BX-K014 • Opinions are those of the authors and not necessarily the U.S. Department of Justice

  3. Objective • Evaluate the Jeol Ltd. AccuTOF DART system as a novel application for use in postmortem toxicology laboratories • Qualitative • Screening methodology • Specifically postmortem • Urine • Blood and tissue

  4. Presentation goals • Equipment set up • Discuss standards run • Urine based testing • Blood/tissue testing • Summary of experience with the instrument • Future work

  5. RTI set up • JEOL TOF • DART • LEAP Technologies CombiPal autosampler • Mass Center software • More recently trying the Schraeder software

  6. Snorkel LEAP Autosampler Ion Source DART AccuTOF DART

  7. How Autosampler Works

  8. Sample Introduction

  9. AccuTOF- DART Strengths • Minimal sample preparation • Broad range of sensitivity • Rapid analysis • Simultaneous determination of multi-drug analytes • Sufficient mass accuracy for formula determination

  10. Reference materials • Examined 112 compounds • drugs and metabolites • Methanolic standard materials • Directly introduced

  11. Isomers

  12. Near Isomers

  13. Urine Method • Drug standards diluted in blank human urine • Glass probe dipped in sample • Analyzed with DART in positive mode • DART temperature @ 300°C • Mass calibrated using polyethylene glycol • Orifice 1 voltage set at 20V • Archived previously confirmed postmortem samples analyzed

  14. Urine Components Urea+H Creatinine Dimer +H Creatinine+H

  15. Cocaine 100 µg/mL M + H = 304.1548

  16. Methamphetamine 100 µg/mL M+H = 150.1278

  17. Triazolam 100 µg/mL M + H = 343.0508

  18. LOD for Drug Analytes in Urine (µg/mL)

  19. Creatinine Issues Oxazepam (10 µg/mL) in DI water (M+H 287.0578) Oxazepam (10 µg/mL) with 10 µg/mL creatinine

  20. Creatinine Issues Oxazepam (10 µg/mL) with 100 µg/mL creatinine Oxazepam (10 µg/mL) with 200 µg/mL creatinine

  21. Archived Case Example EDDP=278.190 278.20765 +17mmu 310.21327 Methadone=310.216 -3mmu

  22. Evaluation of Postmortem Blood and Tissue Samples

  23. “Minimal” Blood/Tissue Method • 2 mL of ACN added to 1 mL of sample • Mixture was shaken and vortexed • Spun in centrifuge at 2500 rpm for 5 minutes • ~100uL of ACN saved for DART analyses • Remainder poured off and dried down at 45°C • Reconstituted in 100 uL of ACN and analyzed

  24. Cases used

  25. Blood method • Acetonitrile added to blood

  26. Blood Method • Vortexed

  27. Blood method • Centrifuged

  28. Blood method • Decanted off supernatant

  29. Blood method • Dry down under N2

  30. Blood method • Reconstitute

  31. SPE method

  32. Human Blood Cholestadiene Monosaccharide Urea Monosaccharide Plasticizer

  33. 310.21838 Methadone 100 ug/mL Methadone in Blank Blood Unextracted M + H =310.216 100 ug/mL Methadone in Blank Blood Extracted in 1:3 ACN

  34. Methadone 100 ug/mL Methadone in Blank Blood Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL 1 ug/mL Methadone in Blank Blood Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL ACN 310. 215

  35. Postmortem Aorta Blood Specimen Un-extracted Previously reported at 2.8 mg/mL Nondetected Extracted in 1:3 ACN

  36. Postmortem Aorta Blood Specimen Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL ACN

  37. Postmortem Liver Specimen Un-extracted Previously reported at 6.6 ug/mL Extracted in 1:3 ACN

  38. Postmortem Liver Specimen Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL

  39. 304.15962 Cocaine 1 ug/mL Cocaine in blank blood extracted in 1:3 ACN M+H=304.154 1 ug/mL Cocaine in Blank Blood Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL ACN

  40. Cocaine 0.1 ug/mL Cocaine in Blank Blood Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL ACN

  41. 304.16913 Postmortem Aorta Blood Specimen Extracted in 1:3 ACN Previously reported at 0.52 mg/mL Extracted in 1:3 ACN/dried/reconstituted in 100 ug/mL ACN

  42. ? BE=290.138 Norpropoxyphene=326.211 Propoxyphene=340.226 Postmortem Cocaine Case • All drugs not found • Could not see without concentrating SPE Extraction

  43. Postmortem case by LC/MS and SPE BE BE-d3 cocaine cocaine-d3 cocaethylene cocaethylene-d3 BE 1253 ng/mL, Cocaine 8.8 ng/mL, CE 2.7 ng/mL

  44. Original case reports

  45. Original case reports

  46. Comparison to “Traditional” MS platforms * No quantitation attempted on the trap ** Source was saturated, resulting in poor quantitation

  47. Table of Drugs Analyzed in PM Specimens a a a a a a a a a a a a a a a a a a

  48. Conclusions • Reasonable sensitivity for some drugs • Greater sensitivity for some drugs over others • Creatinine appears to interfere with ionization of some drugs • Requirement for some sample preparation to mitigate interference from matrix • Auto sampler helps with more consistent sample introduction

  49. Conclusions • At least minimal drug extraction appears necessary to achieve best sensitivity • Extensive (solid phase extraction), does not necessarily improve things

  50. Conclusions • Drug detected in spiked blood have better sensitivity than in postmortem specimens at the same or greater concentrations • Not ideal for detecting therapeutic drug levels • Caveat the post mortem samples used are old and compound degradationmay have occurred

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