Pharmaceutical

In the early stages of drug discovery, a drug candidate needs to be characterized for critical go or no go decision making.  The bottleneck in drug discovery process is the Adsorption, Distribution, Metabolism, Excretion and Toxicology (ADMET) evaluation within a living organism.  Therefore, technology increasing the analytical throughput for such analysis is essential in drug discovery.  By using the LDTD for ADMET studies, you will perform one analysis each 4 seconds increasing dramatically your throughput compared to your current LC-MS/MS method of analysis.  Moreover, many more applications can beneficiate from this analytical speed.

View how the LDTD can increase your drug discovery process

Scientific Publication

• Journal of Pharmaceutical and Biomedical Analysis 2011, 55, pp. 544-551 Simultaneous Quantitation of Metformin and Sitagliptin from Mouse and Human Dried Blood Spots Using Laser Diode Thermal Desorption Tandem Mass Spectrometry, John G. Swales, Richard T. Gallagher, Mark Denn and Raimund M. Peter. DOI:10.1016/j.jpba.2011.02.030.

• Journal of Pharmaceutical and Biomedical Analysis 2011, 54, pp 1088-1095 Laser Diode Thermal Desorption-Positive Mode Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry For The Ultra-Fast Quantification of a Pharmaceutical Compound in Human Plasma, Olivier Heudi, Samuel Barteau, Pierre Picard, Patrice Tremblay, Franck Picard, and Olivier Kretz. DOI:10.1016/j.jpba.2010.11.025.

• Journal of Pharmaceutical and Biomedical Analysis 2010, 53, pp 740-744 Determination of Metformin in Mouse, Rat, Dog and Human Plasma Samples by Laser Diode Thermal Desorption/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry, John G. Swales, Richard Gallagher and Raimund M. Peter. DOI:10.1016/j.jpba.2010.04.033.

• Analytical Chemistry 2007, 79(12), pp 4657-4665  High-throughput Cytochrome P450 Inhibition Assays Using Laser Diode Thermal Desorption-Atmospheric Pressure Chemical Ionization-Tandem Mass Spectrometry, Jin Wu, Christopher S. Hughes, Pierre Picard, Sylvain Letarte, Mireille Gaudreault, Jean-François Lévesque, Deborah A. Nicoll-Griffith, and Kevin P. Bateman DOI: 10.1021/ac070221o.

• _{Note : The results published into the Analytical Chemistry (2007) paper were obtained with a beta-LDTD ion source. Therefore, the laser power reported should not be used with the current LDTD ion source models. Moreover, Phytronix has observed that for more accurate CYP 1A2 results, the probe should be monitor in negative mode. Please refer to the application note 0714 (below) for updated operation conditions.}

Application notes

• AN-1107 4.8 Seconds Sample-to-Sample Analysis In ADME Using LDTD-TripleTOF^TM 5600.
• AN-1106 Extraction and Analysis of Drug on LDTD-384 Platform.
• AN-1105 LDTD-MS/MS Method Validation According to FDA Regulation.
• AN-1003 CACO-2 Permeability Coefficient Determination in LDTD-MS/MS.

• AN-1002 High Throughput Workflow Analysis : Dextrorphan in Human Plasma.

• AN-0706 High Throughput Analysis of 960 Reserpine Samples in 1.9 hours.

• AN-0708 LDTD-MS/MS in 1.8 seconds with RSD of 2.4 % : Paracetamol in Human Plasma Crash.

• AN-0709 Midazolam and 1-Hydroxymidazolam in Human Plasma : LDTD-MS/MS Analysis in 8 Seconds.

• AN-0710 LDTD-MS/MS Analysis in 9 Seconds : Quantification of Mifepristone in Mouse Plasma.

• AN-0714 High Throughput LDTD-MS/MS IC₅₀ Determination of CYP Inhibition in HLM.

Oral Presentations

• Pittcon 2011 Effect of Phospholipids and Formulation Agents in LDTD-MS/MS Analysis of Dextrorphan in Human and Rat Plasma

• ASMS 2010 Evaluation of Phospholipids Effect on Ionization in LDTD-MS/MS Analysis of Human Plasma Extracts from Protein Precipitation, SPE and Liquid-Liquid Extraction

Oral presentation produced by LDTD users

• ASMS 2011 Validation of an Analytical Method to Quantify a Xenobiotic in Rat Plasma Using LDTD-APCI Coupled to Tandem Mass Specteometry (Sanofi-Aventis, France)

• ASMS 2010 High-Throughput LDTD384-MS/MS for Drug Metabolism and Pharmacokinetic Studies (Merck Canada)

Oral presentation produced in collaboration with LDTD users

• ASMS 2010 LDTD384-MS/MS for In Vitro Assays : Different Buffer Environments (in Collaboration with Sanofi-Aventis, France)
  

Posters

• ASMS 2011 Dry Blood Spot Sampling Technology Evaluated for LDTD-MS/MS Analysis.
• ASMS 2011 LDTD-MS/MS in GLP Environment : What Should be Done ?
• ASMS 2011 Speeding up the Dry Blood Spot Sampling With On Step Automated Multiple Extractions Combined with LDTD-MS/MS Analysis.
• ASMS 2009 High Throughput LDTD-MS/MS IC50 Determination of CYP Inhibition in Human Liver Microsome (HLM).
• ASMS 2009 High Throughput Workflow for Midazolam and 1-Hydroxymidazolam Analysis in Human Plasma.
• ASMS 2008 Midazolam and 1-Hydroxymidazolam Determination in Human EDTA Plasma by LDTD/MS/MS in 8 Seconds.
• ASMS 2008 High-Throughput Analysis of Mifepristone and Two Mifepristone Analogues in Mouse Heparin Plasma by LDTD-MS/MS in 9 Seconds.
• ASMS 2007 High-Throughput LDTD-MS/MS Determination of Reserpine : 1000 Samples in Less Than 2 hours.

Posters produced by LDTD users

• ASMS 2011 Quantitation of Small Pharmaceutical Compound by LDTD/MS/MS, Atmospheric Pressure Chemical Ionization, As Compared to LC/MS/MS for Clinical Study Samples. (Abbott Park, USA)
• ASMS 2011 High Throughput Laser Diode Thermal Desorption Mass Spectrometry for the Determination of Time Dependent Cytochrome P450 Inhibition in Human Liver Microsome. (Astra Zeneca, Canada)
• ASMS 2011High-Throughput Caco-2/TC7 Human Intestinal Absorption Screening Using Laser Diode Thermal Desorption - Atmospheric Pressure Chemical Ionization Coupled to Exactive Benchtop Orbitrap (Sanofi-Aventis, France)
• ASMS 2010 Determination of Metformin in Mouse, Rat, Dog and Human Plasma Samples by LDTD-APCI-MS/MS (Astra Zeneca, UK)

• ASMS 2010 Evaluation of Drug Plasma Stability Using an Ultra-High Throughput Laser Diode Thermal Desorption (LDTD) Methodology(Tandem Labs, USA)

• IMSC 2009 Laser Diode Thermal Desorption (LDTD) Mass Spectrometry for High Throughput Analyses of Discovery DMPK In Vitro and In Vivo samples. (Astra Zeneca, Canada)

• ASMS 2009 Validation of Pioglitazone in Human Serum by Two Sample Introduction Methods : LDTD-APCI/MS/MS and LC-ESI/MS/MS. (BASi, USA)

• ASMS 2009 Application of LDTD-APCI-MS to Support Plasma Protein Bonding Study in Drug Discovery. (Pfizer, USA)

Posters produced in collaboration with LDTD users

• ASMS 2009 LDTD-MS/MS Analysis of Eicosanoids and Other Mediators of Inflammation. (in collaboration with Université Laval, Canada)

• ASMS 2009 Analysis of Fatty Acid Methyl Esters Using the High Throughput LDTD Source Coupled to the LTQ Orbitrap Mass Spectrometer. (in collaboratino with IRCM, Canada)

• ASMS 2008 Selected Ion Monitoring (SIM) Mode Data Collection Using the Laser Diode Thermal Desorption (LDTD) Source to Increase Sensitivity. (in collaboration with Thermo Fisher Scientific, USA)

• ASMS 2008 Comparison of Laser Diode Thermal Desorption (LDTD) source vs LC-MS for the analysis of a therapeutic drug in biological extracts. (in collaboration with Astra Zeneca, UK)
• ISSX 2008 Comparison of Various High Throughput Mass Spectrometry-based Technologies to Assess CYP Inhibitions. (in collaboration with Roche, USA)

• ASMS 2007 Application of a Laser Diode Thermal Desorption (LDTD) Ion Source for Mass Spectrometry in a Drug Discovery Environment. (in collaboration with Merk Frost, Canada)

• ASMS 2007 High Throughput Analysis of Testosterone in Human EDTA K2 Plasma. (in collaboration with Anapharm, Canada)