Technology at the speed of light

Transcription

1 Whenever high throughput and speed are required LDTD ion source Technology at the speed of light From ADME to Clinical trials From Food to Environmental From Toxicology to Drug discovery Analysis... from minutes to seconds Distributor:

2 LDTD Highlights Looking for High Throughput Analysis? The LDTD ion source comes in different models depending on the LazWell plate format (96- or 384- wells) and on the mass spectrometers brand it will be attached. The LDTD interface is designed to be a plugand-play ion source as it mimics the actual ion source attached to your mass spectrometer. With one single LDTD you can perform early drug discovery in vitro assays (Permeability, plasma stability and CYP inhibition) as well as bioanalysis, food, environmental and toxicology analysis. Increase your throughput with the ultra fast Laser Diode Thermal Desorption (LDTD) ion source coupled to your mass spectrometer. The LDTD combines an ultra fast laser diode thermal desorption with an efficient gas-phase atmospheric pressure chemical ionization (APCI) to achieve ultra fast sample introduction in mass spectrometry. Eliminate the time consuming chromatographic separation and acquire 1 sample every 4-1 seconds with the LDTD ion source. Integrated to your mass spectrometer, the LDTD operation is easy, intuitive and requires no external software for file acquisition or data processing. Intensity (cps) 5.e4 4.8e4 4.6e4 4.4e4 4.2e4 4.e4 3.8e4 3.6e4 3.4e4 3.2e4 3.e4 2.8e4 2.6e4 2.4e4 2.2e4 2.e4 1.8e4 1.6e4 1.4e4 1.2e4 1.e Time (min) LDTD-MS/MS thermal desorption peak showing the speed of analysis with excellent peak-to-peak resolution and reproducibility (n=12). The analysis was performed within 18 seconds System Traceability and Autonomy The LDTD ion source is equipped with a 1 plates loader which can be reloaded while being in operation for a workday autonomy. A barcode reader integrated into the LDTD provides a complete sample traceability and eliminates the risk of wrong sample analysis. Low Maintenance System The LDTD is operated only with compressed air no more solvent to handle, no more tubing to inspect, no more leak to take care of. The LDTD design reduces the maintenance and minimizes instrument services as compared to mobile phase introduction based techniques.

3 LDTD Principle of Operation Step-by-step From your sample preparation plate to the Lazwell plate as easy as that LazWell Sample Plate Carrier Gas IR Laser Beam Transfer Tube Mass Spectrometer Inlet Piston head Piston Corona Discharge Needle Once the sample is introduced into the 96 or the 384- LazWell, the typical 1 to 2 µl of solvent is evaporated and the plate is ready to be run. The dried sample is thermally desorbed by the indirect action of a laser diode irradiating on the back-side of the sample holder. The thin stainless steel sheet instantly transfers the heat to the sample which undergo thermal desorption producing gas phase neutral molecules. A constant air stream carries the desorbed neutral molecules through the transfer tube into the corona discharge to undergo APCI. The formed ions enters the mass spectrometer for their detection. All this process within 1 seconds. Features The LDTD design allows an ultra fast thermal desorption at an unattended low temperature minimizing the occurrence of thermal fragmentation. The use of an unheated transfer tube also minimizes thermal fragmentation, and eliminates the carryover. The gas-phase APCI (as operated without mobile phase) allows an efficient ionization by a direct proton transfer from water clusters formed into the corona discharge to your analyte. Moreover, this solvent free APCI is robust to ion-suppression as compared to ESI based introduction system. Shotgun approach Full integration into most popular MS Softwares Versatile Plug-and-Play Interface LDTD plate loader for walk-away convenience Barcode reader for sample traceability No pump, tubing, fluid, valve, leak no problems Low maintenance system PHYTRONIX 3

4 LDTD Software Integration The LDTD is operated directly from your mass spectrometer software. Configure the LDTD ion source and your samples, run your samples, as simple as that You don t need to learn new softwares, or concern yourself with data transfer. You simply build a batch sequence as usual and run your sample with the LDTD ion source attached to your mass spectrometer. With the LDTD ion source, you can run multiple MS methods and multiple laser conditions within the same sample batch sequence for optimization. LDTD Plug-and-Play Interfaces S-96/S-384 For your Sciex mass spectrometers Companion software into Analyst T-96/T-384 For your ThermoFisher mass spectrometers Instrument configuration into XCalibur WX-96/WX-384 For your Waters mass spectrometers Inlet configuration into MassLynx

5 LDTD Applications In Vitro Analysis % Metabolite Perform In vitro ADME assays with the LDTD and increase your laboratory s productivity in running your samples under generic conditions. Cytochrome P45 inhibition assays Combine the specificity of the MS/MS configuration with the LDTD speed of analysis for CYP inhibition assays. Identify drug-drug interactions (DDI) using the LDTD ion source to run your CYP inhibition assays using the FDA recommended drug probes and inhibitors from your quenched assay plates. Get your Time- and Concentration-Dependent inhibition assays done by the time required to run a single sample using chromatographic-based techniques Testosterone (CYP 3A4) LCMS UPLC LDTD Log [Concentration, ( M)] Ptot LDTD (1-7 cm.s -1 ) y = 1,296x R 2 =, Ptot UPLC (1-7 cm.s -1 ) Correlation of Caco-2/TC-7 permeability results for 125 new drug candidates determined in LDTD-MS/MS and UPLC-MS/MS Rencontre du GMP meeting, Paris, France, Septembre 21. Julian et al. Assessment of LDTD-MS/MS in Early in vitro and in vivo ADMET : CaCo2, Cytochrome P45 competitive inhibition and early PK. ADME to Clinical Trials Permeability Assays CYP inhibition Assays Plasma Stability Pharmacokinetic Studies Dried Blood Spot Analysis CYP3A4 inhibition curve with kenoconazole as inhibitor and OH-testosterone monitored as drug metabolite. The LDTD run-time was 6 sec. while it was 252 sec. in LC-MS/MS and 12 sec. in UPLC-MS/MS. The calculated IC5 values were all matching within each other. ISSX 28, San Diego, USA, He et al., Comparison of Various High Throughput Mass Spectrometry-based Technologies to Assess CYP Inhibitions. (in collaboration with Roche, USA). CYP Inhibitor Drug probe 1A2 2A6 2B6 2C9 2C19 2D6 2E1 3A4/5 furafylline α-naphthoflavone tranylcypromine tranylcypromine sulfaphenazole ticlopidine quinidine clomethiazole ketoconazole phenacetin, melatonin, tacrine coumarin bupropion tolbutamide, diclofenac S-mephenytoin dextromethorphan, bufurolol chlorzoxazone midazolam, testosterone, nifedipine 5PHYTRONIX

6 LDTD-High Resolution MS the exact mass at the speed of light With a LDTD-High Resolution MS system, forget about multi-variable optimization. Run your samples under generic LDTD conditions monitoring the new drug candidates Exact Masses for your Plasma Stability, Protein Binding and Plasma Stability assays. % Remaining LDTD % Bound Time (min) Rat (blue) and Human (red) plasma stability assay of procaine performed in LDTD-MS/MS. 5 LC % Bound Correlation between LDTD-MS/MS and LC-MS/MS results for plasma protein binding assay ASMS meeting, June 29, Philadelphia, USA, Tan et al. Application of LDTD-APCI-MS to Support Plasma Protein Binding Study in Drug Discovery. ASMS meeting, June 21, Salt Lake City, USA, Ho et al., Evaluation of Drug Plasma Stability Using an Ultra-High Throughput Laser Diode Thermal Desorption (LDTD) Methodology. In Vivo Applications With the LDTD ion source, get accurate, precise and reproducible data for your plasma samples analysis and get your pharmacokinetic parameters faster than ever. The high throughput nature of the LDTD ion source will speed up your clinical trials. Accelerate the drug discovery process by eliminating the MRM optimization and the bottleneck of chromatographic separation Achieve unprecedented high speed and accurate mass for drugs and metabolites screening LDTD-APCI-MS/MS y = 1.286x R 2 = LC-MS/MS Correlation between LDTD-MS/MS and LC-MS/MS of a new drug candidate concentration determined in clinical plasma samples (n=3). LDTD-MS/MS run-time of 9 seconds as compared to a 7 minutes LC-MS/MS run-time. Heudi et al. Journal of Pharmaceutical and Biomedical Analysis, 211, vol. 54, p

7 Toxicology Analysis With the LDTD, your What if... is transformed in What's next! What if you could perform drug of abuse testing them in less than 1 seconds per sample... This is exactly what the LDTD can do on a day-to-day basis. Drug testing in urine and plasma are achieved using LDTD ionization source and are 5 times faster than any data published. Fast screening combined to accurate quantification results will allow your laboratory to increase your analytical capacity and reduce your turnover time.. Food Analysis In a world where quality control and health issues are so important to our society, very fast methods for food analysis are needed. The food industry has its own concerns to ensure protection for everyone. Complex matrix such as food is quite a challenge to any analytical system. The robustness of the LDTD and its speed are ready for this kind of challenge in allowing, for example, the analysis of dairy milk and honey for antibiotic residues without extensive sample preparation. Environmental Analysis Being "green by nature", LDTD and environmental analysis are a natural match. BTEX analysis in urban air, endocrine disrupting chemicals and antibiotics identification in surface water show how the LDTD can performs traces analysis in environmental matrix. From Toxicology to Forensic Analysis K2, Spice Natural and Synthetic Opiates Benzodiazepines Street Drugs And many more The high throughput nature of LDTD/APCI-MS/MS method alleviate the clinical sample analysis and therefore speed up the clinical trials process. Heudi et al., Journal of Pharmaceutical and Biomedical Analysis, 211 vol. 54, p The technique (LDTD) has great potential within the pharmaceutical industry not only for in vivo analysis but also for use as a rapid sample introduction technique for in vitro experiments such as absorption and solubility assays which often screen many hundreds of compounds per week. Swales et al., Journal of Pharmaceutical and Biomedical Analysis, 211, vol. 55, p PHYTRONIX 7

8 LDTD evaluation The best way to discover if the LDTD ion source is right for you is to conduct an evaluation with your application(s) in mind. Choose the approach that is right for you: 1 2 Run your samples at our Demo Lab in Quebec city which is housed with the most common makes of triple quadrupoles mass spectrometers, in 96-well or 384-well plate format interface. A report will be generated according to agreed evaluation criteria. We invite you to join us at our Demo Lab to show you the highest level of development achieved in highthroughput analysis. We come to your site for an Onsite LDTD evaluation. The LDTD ion source is shipped to your facility. A Phytronix scientist performs the system installation, provides LDTD training, and collaborates with you for up to one (1) week in your method validation. After this initial week, the LDTD ion source will be yours for up to three (3) weeks for additional runtime (use) and evaluation at no charge. The only charges are for LazWell plates used during the evaluation period. All LDTD models are available for Onsite evaluation. Distributor: ERC GmbH Phytronix Technologies Parc technologique du Québec Fax métropolitain partner@erc-hplc.de 4535, boulevard Wilfrid-Hamel, suite 12, Québec (Qc) Canada G1P 2J7 P F info@phytronix.com All product and company names mentioned herein may be the trademarks or registered trademarks of their respective owners. Phytronix shall not be liable for errors contained herein or for incidental or consequential damages in connection with the use of this material. Information, description and specifications in this publication are subject to change without notice. Phytronix Technologies, Inc Imprimé au Canada Printed in Canada