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Exactive LC- MS for
Quantitation in Clinical and
Forensic Toxicology Research
For Clinical Research and Forensic Toxicology Use Only
Overview
 Exactive As a Quantitative Analysis Tool
 Clinical and Forensic Toxicology Research Methods
 Drugs Supported in the Methods
 Quantitation Workflow
 What You Don’t Have To Do
 Why it is Easy To Use
 User Testimonials
 Proof Statements and Support
 Summary
 Appendix
For Clinical Research and Forensic Toxicology Use Only
2
Why Consider Exactive For Quantitation
LOQ, Precision and Dynamic Range ~ Mid to High End QQQ
QQQ Assays Plus More
Easiest to Use
Ideal for Analytes
with
Poor Fragmentation
Large Panel of Drugs
in
Single Assay
Sample Prep Requirement
Same As QQQ
Good Screening Capabilities
Unbeatable Price/Performance
For Clinical Research and Forensic Toxicology Use Only
3
Why Consider Exactive For Quantitation
Methods
Forensic Tox Research
Clinical Research
ETG/ETS
in Urine
Immunosuppressant
Drugs in
Whole Blood
Opioids
Benzodiazepines
in Urine
Vitamin D3
in Plasma
Opiates
in Urine
10 Steroid Panel
in Plasma
Drugs of Abuse Screening
For Clinical Research and Forensic Toxicology Use Only
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Why Consider Exactive For Quantitation
Forensic Research
Clinical Research
Immunosuppressant Drugs
Serolimus
Tacrolimus
Everolimus
Cyclosporin A
ETG/ETS
Benzodiazepines
Lorazepam
Nordiazepam
Hydroxytriazolam
Aminotriazepam
Aminoflunitrazepam
Hydroxyethylflurazepam
Vitamin D3
25 OH Vit D3
25 OH Vit D2
Diazepam
Temazepam
Aminoclonazepam
Hydroxyalprazolam
Desalkylflurazepam
Oxazepam
10 Steroid Panel
Aldosterone
Androstenedione
Corticosterone
Cortisol
Deoxycortisol
Dehydroepiandrosterone sulphate
Progesterone
17 alpha-hydroxyprogesterone
Testosterone
Opiates
Morphine, Hydromorphone, Oxymorphone
Codeine, Dihydrocodeine, Hydrocodone
Oxycodone, Meperidine, Normeperidine
6-Acetylmorphine
Drugs of Abuse Screening
For Clinical Research and Forensic Toxicology Use Only
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Opioids
Norketamine
Ketamine
Nalbuphine
Norfentanyl
Fentanyl
Butorphanol
Alfentanil
Sufentanil
Exactive Quantitation Workflow
What You Do
Sample
Preparation
Urine Dilute n Shoot
or
As
Easy
As
It
Can
Get
Turbo Flow
or
LLE
Data Acquisition
LC - Exactive
Full Scan MS@ 50 100K resolution using
HESI or APCI source
Mass Range 504000m/z
Data Processing
Extract data for
compounds and internal
standards using better
than 2ppm mass
accuracy
or
SPE
Quantitate
Report Results
What You Don’t Have To Do (next slide)
For Clinical Research and Forensic Toxicology Use Only
6
Quantitate using peak
area of extracted ion
chromatograms for
samples and calibrators
Exactive Quantitation Workflow
What You Don’t Have To Do
Optimize SRM’s
Infusion or FIA optimization
Painstaking process of product ion
selection for best sensitivity and specificity
Collision gas optimization
Optimization of ion path lens voltages
Optimization of Timed SRM
For Clinical Research and Forensic Toxicology Use Only
7
Exactive Quantitation Workflow
Why it is Ease to Use
Easiest to operate
No SRM optimization
Quantitate large panels without
additional optimization considerations
Easiest to expand assay
Easiest to interpret data
Easiest to maintain
For Clinical Research and Forensic Toxicology Use Only
8
What Do Users Say
“The beauty of the Exactive MS is that it allows us to look for unknown
metabolites at the same time that we quantitate known metabolites. In our
laboratory, we have been able to identify four different fentanyl metabolites with
no need for UV detection, fraction collection with NMR, or MS/MS
fragmentation patterns”
Uwe Christians, MD, PhD, Professor, Department of
Anesthesiology, University of Colorado and iSiS Clinical Research &
Development Lab Director
“We historically used triple quadrupole mass spectrometers but were very
impressed with the Exactive demo. After acquiring the system, we had to do
little to no method development. It’s flexibility in analyzing both dilute-and-shoot
and SPE prepared samples and the ease of addition of new compounds to our
drug panels helped us keep things simple. Overall, it turned out to be a wise
choice for our Drugs of Abuse and Pain Management drug analyses”
Kent Johnson, Director
Fortes Lab, Portland Oregon, USA
For Clinical Research and Forensic Toxicology Use Only
9
Proof Statements and Support
 Performance and Method Details (PPT files for each method)
 Library of Compounds for Screening in ToxID
 Assay Installation and Training
 Customer Reference Sites
For Clinical Research and Forensic Toxicology Use Only
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Summary
All Things Considered, Ultrahigh Resolution
Exactive Bench Top LC/MS System Is a Very
Efficient and Sensitive Alternative Quantitation Tool
for Use in Clinical and Forensic Research
Including Pain Management.
For Clinical Research and Forensic Toxicology Use Only
11
Appendix
For Clinical Research and Forensic Toxicology Use Only
12
Exactive Quantitation Workflow
 Why is it easy to use
• Easiest to operate
• Full scan MS operation
• No SRM optimization
• Monitor m/z of interest at ultrahigh resolution and mass accuracies
• Monitor large panels without additional optimization considerations
• Just extract m/z of interest in any full scan MS acquisition
• Easiest to expand assay
• Full scan acquisition means all ions all the time
• Easiest to interpret data
• Just need to know the m/z of the compound of interest
• Easiest to maintain
• Less complex ion path, no collision cell and the necessary gas.
For Clinical Research and Forensic Toxicology Use Only
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