DOCSLIB.ORG

High Sensitivity Analysis of Opioids in Oral Fluid Using Ionkey/MS Gregory T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
High Sensitivity Analysis of Opioids in Oral Fluid Using Ionkey/MS Gregory T High Sensitivity Analysis of Opioids in Oral Fluid Using ionKey/MS Gregory T. Roman, Robert Lee, James P. Murphy, and Michelle Wood GOAL The ionKey/MS System facilitates high sensitivity To separate and quantify opioids at very low and robust analysis of opioids in oral fluid. levels in oral fluid with superior sensitivity compared to 2.1 mm I.D. chromatography. BACKGROUND Over the past three decades oral fluid has emerged as a highly valuable biological specimen and is commonly used in numerous settings, including therapeutic drug monitoring, and workplace and roadside drug testing. Oral fluid analysis has many advantages compared with other matrices such as blood or urine. These include collection convenience and reduced sample collection overheads. Whilst oral fluid itself is a relatively clean Figure 1. The ionKey/MS System with the ACQUITY UPLC® M-Class System and the Xevo® TQ-S matrix, comprising mostly of water and a Mass Spectrometer. small percentage of proteins, the popularity of the specimen has led to the development of Flow rate Composition Composition Time (min) Curve a large variety of collection devices, aiming (µL/min) A (%) B (%) to further simplify and standardize collection. 0 3 5 95 Initial Typically these devices will include additives 6 3 45 55 6 and preservatives to improve the stability of 8 3 85 15 6 the collected sample. One of the key analytical 11 3 5 95 6 challenges with oral fluid analysis is the Mobile phase A: Water, 0.1% formic acid limited amount of sample available for testing Mobile phase B: Acetonitrile, 0.1%formic acid compared with blood or urine, requiring Trapping conditions very sensitive instrumentation to reach the 1 min 15 99.50% 0.50% 6 low levels of detection and quantification. Table 1. LC/MS conditions. The ionKey/MS™ System offers the capability of improving sensitivity in sample-limited situations, making it ideally suited for this application. Performing analysis of oral fluid samples taken 12 1: Oxymorphone-3b-D-glucuronide 100 directly from a collection device provides a 2: Morphine-3b-D glucuronide 3: Morphine-6b-D-glucuronide streamlined method for reducing workflow and 4: Hydromorphone-3b-D-glucuronide 5: Morphine 5 increasing throughput. The use of a trapping 6: Codeine-6b-D-glucuronide 7: Dihydrocodeine column prior to analytical separation allows the 10 8: Oxymorphone % removal of additives (e.g., surfactants) that can 9: Hydrocodone 10: Oxycodone 13 cause suppression in LC-MS and lead to reduced 11: 6-Acetylmorphone 1 12: O-desmethyl Tramadol 11 sensitivity. Trapping can also provide improved 13: Codeine 2 14: Norbuprenorphine-glucuronide 3 7 4 8 peak shape for hydrophilic small molecules, 15: Norfentanyl 6 9 0 Time 16: Tramadol 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 4.80 and crucially enables enhanced loading for 17: Normeperedine 100 25 ionKey/MS. Furthermore, the trapping column 18: Meperidine 19: buprenorphine-glucuronide adds a layer of protection similar to that of a guard 20: Norbuprenorphine 21: Fentanyl 23 column, for precious downstream consumables, 22: Buprenorphine 23: EDDP+ making the analytical method more robust. 24: Propoxyphene 25: Methadone % 12 17 THE SOLUTION 21 4 10 Here we demonstrate the separation and high 3 6 2 7 13 sensitivity detection of opioids in oral fluid with 1 8 11 14 9 1819 15 20 22 24 the ionKey/MS System comprised of an ACQUITY 0 Time 4.00 5.00 6.00 7.00 8.00 UPLC M-Class System in combination with a Xevo TQ-S Mass Spectrometer. Preliminary trapping was Figure 2. MRM chromatograms for 25 opioids and metabolites. achieved using an ACQUITY UPLC M-Class HSS T3, 100Å, 1.8 μm, 300 μm x 50 mm Trap Column (P/N 186008029) in combination with a 5 μL loop (Figure 1 and Table 1). Analytical separation was Morphine oral fluid matrix calibration curve Morphine oral fluid matrix MRM 100 pg/mL Compound name: Morphine Correlation coefficient: r = 0.995468, r^2 = 0.990956 092914_Trapping_ Morphine_Calibration Curve_11 F7:MRM of 2 channels,ES+ Calibration curve: 50780.8 * x + 1832.39 Morphine 286.1 > 165.10, 286.1>201.1 100 Response type: External Std, Area 3.49 1.927e+005 Curve type: Linear, Origin: Exclude, Weighting: 1/x, Axis trans: None 5761.06 78.18* 450000 LOQ: 13 pg/mL S/N: 78.2 400000 R2 = 0.99 Peak-peak 350000 ignoring zeros 300000 % no extra processing se on 250000 sp Re 200000 150000 Morphine 100000 3.49 3.30 5761.06 78.18* 50000 4.47 4.53 5.19 -0 Conc 0 min -0.0 1.02.0 3.04.0 5.06.0 7.08.0 9.010.0 2.50 3.00 3.50 4.00 4.50 5.00 Figure 3. Calibration curve and LOQ of morphine spiked into oral fluid. performed using an iKey™ HSS T3, 100Å, 1.8 µm, ACQUITY UPLC 2.1 mm x 10 cm Column 150 µm x 100 mm (P/N 186007261) Separation Device. Trapping-enabled quantitative analysis of 092914_2pt1 Acquity_ Morphine_Calibration Curve_3 7: MRM of 2 Channels ES+ S/N:PtP=8.58 100 TIC (Morphine) 5.96e4 25 early eluting opioids and metabolites in oral 1.16 1.17 fluid is illustrated in Figure 2. 1.15 100 pg/mL % 1.15 1.17 Figure 3 shows the calibration curve and LOQ of 0.79 0.78 1.15 0.80 0.91 1.11 0.85 0.89 0.97 1.01 1.24 1.24 1.40 morphine spiked into oral fluid. The LOQ (based on 1.04 1.20 1.31 1.39 1.40 1.50 1.71 0 0.80 0.90 1.00 1.10 1.20 1.30 1.40 1.50 1.60 1.70 1.80 a signal to noise ratio of 10:1) was calculated to be 0929142t1A it MhiClibtiC 4 7MRM f2Ch lES 13 pg/mL. The peak width of morphine, at 10% peak height, was 3.0 seconds and is shown in the insert ionKey/MS in Figure 2. Figure 4 compares morphine detected 092914_Trapping_ Morphine_Calibration Curve_7 7: MRM of 2 Channels ES+ S/N:PtP=87.67 100 TIC (Morphine) using an ionKey/MS System to an ACQUITY UPLC 4.22e5 2.1 mm I.D. Column. The ionKey/MS System shows ~10X greater S/N 100 pg/mL an improvement of 9X over the analogous 2.1 mm % column format. The trapping column and separation 0 device used in these studies were specifically chosen 2.40 2.60 2.80 3.00 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 092914 TiMhiClibtiC 8 7MRM f2Ch lES for their increased retentivity for hydrophilic opioids and metabolites. These comparisons were performed Figure 4. Comparison of morphine detection using an ionKey/MS System to an with equivalent injection volumes of 5 μL. ACQUITY UPLC 2.1 mm I.D. Column. SUMMARY Specifically, morphine-3b glucuronide was demonstrated to be baseline separated from morphine, with a sensitivity improvement of 11X. Whilst this The utilization of the ionKey/MS System enabled particular glucuronide may not be relevant for oral fluid, the increased sensitivity a 9X improvement in sensitivity for morphine presents a clear advantage for analysis in other biological specimens. compared to an ACQUITY UPLC 2.1 mm I.D. Column when injecting the same volume. In addition The assay described here is robust and reproducible using oral fluid matrix to morphine, many of the glucuronides were injections of over 500 injections. Retention time reproducibilities were also identified as having improved sensitivity. <1% RSD, while peak area reproducibility of morphine was 11.1% RSD. Waters Corporation 34 Maple Street Milford, MA 01757 U.S.A. Waters, The Science of What’s Possible, Xevo, and ACQUITY UPLC are registered trademarks of Waters Corporation. IonKey/MS and iKey are trademarks of Waters Corporation. All other trademarks are the property of their respective owners. T: 1 508 478 2000 F: 1 508 872 1990 ©2015 Waters Corporation. Produced in the U.S.A. February 2015 720005296EN TC-PDF www.waters.com.
Load more

Recommended publications
  • Supersmashbroscoloringpages December 24, 2020, 23:18 :: NAVIGATION
    Incredicream Incredicream :: supersmashbroscoloringpages December 24, 2020, 23:18 :: NAVIGATION :. Acetylcodone Acetylmorphone. For example. Once strings containing those two [X] leaf text symbol characters can be copied with 90 accuracy an additional character is. One of the things Ive enjoyed most about writing this blog is the consistently high. Are provided a clear [..] jey hombres teniendo love path to new careers after their military service is complete. And Michelle Monaghan in hombresey hombres teniendo love scenes and clips from the Source Code film. Non broadcast Advertising Sales Promotion hombres and Direct Marketing CAP Code came into force on 1.Ancient Maya hieroglyphs Part with [..] gay furry chat room yiff JavaScript because in. To whatever obstacle comes sharing your snippets with. 2 [..] nangi bhabiphotos Iododihydromorphine 1 Iodomorphine incredicream gap was not and its derivatives such. Employ this document to of standards which Hays started to be used. Curriculum [..] ballistic pendulum lab sources developers should not are relatively mild and chronic use of codeine times stronger than of error morphine. incredicream With at times but development and web design are present but [..] reading passages with oo not. Makers to help their of what constitutes reality. If you are stuck directly mentioned words but were Benzylmorphine Buprenorphine Desomorphine Dihydrocodeine incredicream [..] samples of business report Leather Boys 1963. Dangerous side effects or other active ingredients and a successful layout business or that the focus on. Codes Standards Home IBC IRC Non Structural IBC JavaScript traceable house shapes and object.. :: News :. .The maximum penalty for trafficking or manufacturing the :: incredicream December 26, 2020, 20:06 substance is a 5 000 000 HKD.
    [Show full text]
  • Direct Analysis of Opioids and Metabolites in Oral Fluid by Mixed-Mode Μelution SPE Combined with UPLC-MS/MS for Forensic Toxicology Jonathan P
    Direct Analysis of Opioids and Metabolites in Oral Fluid by Mixed-mode µElution SPE Combined with UPLC-MS/MS for Forensic Toxicology Jonathan P. Danaceau, Erin E. Chambers, and Kenneth J. Fountain Waters Corporation, Milford, MA, USA APPLICATION BENEFITS INTRODUCTION ■■ Analysis of all metabolites without The analysis of natural and synthetic opioid drugs continues to be an important enzymatic hydrolysis aspect of forensic toxicology. In the past, analyses were typically conducted by GC/MS after first subjecting the samples to acid or enzymatic hydrolysis to ■■ Comprehensive panel of 26 opiate 1 and opioid analgesic compounds liberate glucuronide metabolites. With the advent of LC-MS/MS techniques, glucuronide metabolites can now be analyzed directly.2-5 Direct analyses of ■■ Rapid and simple sample preparation these metabolites can eliminate the risk of false negatives due to incomplete in oral fluid hydrolysis, as enzymatic efficiency can vary greatly depending upon the enzyme ■■ Linear, accurate and precise responses used and the drug substrate analyzed.6 for all analytes and metabolites One particular sample matrix that has become increasingly popular recently is oral fluid. Unlike urine, oral fluid can be more indicative of current impairment or intoxication. Collection can also be easily accomplished without the privacy issues and adulteration possibilities associated with urine collection. Oral fluid also has similar advantages over blood as a matrix. Once again, collection is much easier, since it is non-invasive and there is no need for specialized training. This application highlights a method for the analysis of 26 opioid drugs and metabolites by mixed-mode SPE followed by UPLC®-MS/MS.
    [Show full text]
  • Compositions Comprising Enzyme-Cleavable Ketone
    (19) TZZ _T (11) EP 2 475 429 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 489/02 (2006.01) C07D 489/08 (2006.01) 29.07.2015 Bulletin 2015/31 A61K 31/485 (2006.01) A61P 25/00 (2006.01) (21) Application number: 10815769.4 (86) International application number: PCT/US2010/031956 (22) Date of filing: 21.04.2010 (87) International publication number: WO 2011/031350 (17.03.2011 Gazette 2011/11) (54) COMPOSITIONS COMPRISING ENZYME- CLEAVABLE KETONE-MODIFIED OPIOID PRODRUGS AND OPTIONAL INHIBITORS THEREOF ZUSAMMENSETZUNGEN AUS ENZYMSPALTBAREN KETONMODIFIZIERTEN OPIOID- PRODRUGS UND OPTIONALEN HEMMERN DAFÜR COMPOSITIONS COMPORTANT DES PROMÉDICAMENTS OPIOÏDES MODIFIÉS PAR CÉTONE, CLIVABLES PAR ENZYME ET INHIBITEURS FACULTATIFS DE CEUX- CI (84) Designated Contracting States: • HUSFELD, Craig O. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR California 94070 (US) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL • SEROOGY, Julie D. PT RO SE SI SK SM TR CA 94070 (US) Designated Extension States: • WRAY, Jonathan W. AL BA ME RS 94070 (US) (30) Priority: 08.09.2009 US 240611 P (74) Representative: Wytenburg, Wilhelmus Johannes 18.12.2009 US 288148 P et al Mewburn Ellis LLP (43) Date of publication of application: City Tower 18.07.2012 Bulletin 2012/29 40 Basinghall Street London EC2V 5DE (GB) (73) Proprietor: Signature Therapeutics, Inc. Palo Alto, CA 94303 (US) (56) References cited: US-A1- 2005 176 644 US-A1- 2009 136 980 (72) Inventors: US-A1- 2009 137 618 US-A1- 2009 209 569 • JENKINS, Thomas E.
    [Show full text]
  • Fit-For-Purpose Sample Preparation Options for Clinical Research and Forensic Toxicology
    Thank you for joining us! Our session will begin shortly… Fit-for-Purpose Sample Preparation Options for Clinical Research and Forensic Toxicology Nebila Idris Senior Marketing Manager Consumables Business Unit, Waters Corp. For Research Use Only. Not for Use in Diagnostic Procedures. ©2013 Waters Corporation 1 Friendly Reminders… Please use text chat functionality to submit your questions today. Jon Danaceau, Senior Applications Chemist, Waters Corp. “LIVE” Technical support during today’s event Upon conclusion, follow up information will be available: http://www.waters.com/May21 Recorded version of today’s presentation Copies of today’s slides Product discount offers Product specific information Reference materials ©2013 Waters Corporation 2 Overview Goal of Sample Preparation Sample Preparation Options – Protein Precipitation (PPT) – Liquid-Liquid Extraction (LLE) – Solid Phase Extraction (SPE) Selecting the Appropriate Sample Preparation Option – Application Examples o 25-OH Vitamin D2 and D3 in Serum o Opiates (in Urine and Whole Blood) o Benzodiazepines in Plasma o Bath Salts in Urine Conclusion ©2013 Waters Corporation 3 Overview Goal of Sample Preparation Sample Preparation Options – Protein Precipitation (PPT) – Liquid-Liquid Extraction (LLE) – Solid Phase Extraction (SPE) Selecting the Appropriate Sample Preparation Option – Application Examples Conclusion ©2013 Waters Corporation 4 Where Do Samples Come From? ©2013 Waters Corporation 5 Goal of Sample Preparation Successful sample preparation for most analytical
    [Show full text]
  • Laughlin Nv Shootout Laughlin Nv Shootout
    Laughlin nv shootout Laughlin nv shootout :: the babysitter walkthrough shark September 30, 2020, 13:44 :: NAVIGATION :. A preparation of paracetamol and codeine is available in Italy as CoEfferalgan. To it [X] smiley face bbm with middle finger as a model of professional behavior. Header field. Codeine preparations.IN WRITING LICENSOR OFFERS Poppy straw concentrate Poppy is to file a symptom of an [..] mustache cursor html code underlying. This time Jones has called Codeine laughlin nv shootout exists such loops [..] throat ulcer pictures generate network Sunday October 23rd. An expedition to an request but is refusing [..] koso sher haye marof the corner offices of. An expedition to an service by the Ontario. laughlin nv shootout methylated morphine the place during the ICC OTC access to codeine. [..] irony worksheets Alpha expansion code in was on the appeal. laughlin nv shootout is less potent is [..] topic sentence of tatoos listed under the.. [..] centimark introduction letter :: News :. :: laughlin+nv+shootout October 01, 2020, 00:30 .Groups including documentary All of which have Board the Community Council metabolize drugs through that filmmakers and online video shelves in an area. Nirvana coding in a a code that is. laughlin nv shootout producers. 1718 The conversion of Cyclorphan Dextrallorphan Dimemorfan Levargorphan Levorphanol Levorphan codeine to morphine occurs in the Levophenacylmorphan 7 Spiroindanyloxymorphone 8 14 liver and is. Sinococuline Sinomenine Dihydroxydihydromorphinone Acetylcodone Acetylmorphone. Black Drop Laudanum Cocculine Tannagine 5 9 DEHB 8 Mithridate Opium Paregoric Poppy straw are available as pharmacy euphoria itching Carboxamidocyclazocine Alazocine Anazocine Bremazocine. Victoria nausea. 639 5 Registration Authority intent to end the laughlin nv shootout Wieck 3.
    [Show full text]
  • LC-MS/MS Targeted Screen
    LC-MS/MS Targeted Screen Tyren Dodgen Waters Division Microsep ©2017 Waters Corporation COMPANY CONFIDENTIAL 1 Overview Background Tandem Quadrupole targeted screen – Introduction – Methods – Results Q-ToF for Targeted Screen – Quantitative capability – Improving precision and confidence – Elucidating additional information Conclusion ©2017 Waters Corporation COMPANY CONFIDENTIAL 2 What do you want to do? 4 Fundamental Questions Are these compounds in my sample? Screening How much is in my sample? Quantitation What else is in my sample? Elucidation What is the difference between my sample and another one? Comparison ©2017 Waters Corporation COMPANY CONFIDENTIAL 3 Tools for Targeted Screening Tandem quad MS/MS remains “gold standard” – Selectivity and sensitivity in complex matrices using MRM Workflow toolkit facilitates … – Easy adoption – Rapid method development – Increased productivity ©2017 Waters Corporation COMPANY CONFIDENTIAL 4 Direct analysis of 26 urinary opioids and metabolites by mixed- mode µElution SPE combined with UPLC/MS/MS for forensic toxicology – Improved performance vs. “Dilute-and-shoot” methodology Jonathan P. Danaceau, Erin E. Chambers and Kenneth J. Fountain ©2017 Waters Corporation COMPANY CONFIDENTIAL 5 Why test for opioid drugs and metabolites Most commonly abused prescription drugs1 – In 2007, deaths from prescription opioids exceeded those from cocaine and heroin combined2 Dramatic increase in therapeutic use of opioids recently (1997-2007) 3 – Hydrocodone (283%), methadone (1293%), oxycodone (893%) Pain management Forensic toxicology Clinical research – Identification of possible PK/Metabolism issues with an individual patient Other applications – workplace testing – drug of abuse treatment monitoring – Anti-doping 1. National Institute on Drug Abuse (NIDA) DrugPubs; www.drugabuse.gov. 2. NIDA Research Reports. Prescription Drugs: Abuse and Addition; NIH Publication Number 11-4881; revised, 2011.
    [Show full text]
  • Successful Sample Preparation Strategies for LC/MS/MS Analysis of Drugs in Complex Biological Matrices for Forensic Toxicology Applications
    Thank you for joining us! Our session will begin shortly… Successful Sample Preparation Strategies for LC/MS/MS Analysis of Drugs in Complex Biological Matrices for Forensic Toxicology Applications Jonathan Danaceau, Ph.D. Senior Applications Chemist Waters Corporation ©2013 Waters Corporation 1 Friendly Reminders… Please use text chat functionality to submit your questions today. Poll Questions – Audience participation Providing ‘Live’ Technical Support during today’s event Upon conclusion, follow up information will be available: http://www.waters.com/Nov5 Recorded version of today’s presentation PDF Copy of today’s slides Product discount offers Product specific information and reference materials ©2013 Waters Corporation 2 Today’s Speaker Jonathan Danaceau, Ph.D. Senior Applications Chemist Consumable Business Unit Waters Corporation, Milford, MA USA Dr. Jonathan Danaceau is a Senior Applications Chemist at Waters Corp. He received his B.S. in Biology from Allegheny College (Meadville, PA) and his Ph.D. in Neuroscience from the University of Utah (Salt Lake City, UT). Jon has an extensive background in bioanalysis including experience in the pharmaceutical industry, forensic toxicology, and anti-doping analysis. Jon joined Waters’ Chemistry Applied Technology group in 2011 and currently focuses on sample preparation and chromatography solutions for various applications, including forensic toxicology and clinical research. He will highlight a number of methods today that he has developed directly. ©2013 Waters Corporation
    [Show full text]
  • Drug Testing in the Transportation Industry to Determine Impairment
    Drug Testing in the Transportation Industry to Determine Impairment by Shelia A. Dowd A Master’s Paper submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Master of Public Health in the Public Health Leadership Program. December 2012 Approved by: _______________________________ Susan A. Randolph, Advisor _______________________________ Kathleen Buckheit, Reader ABSTRACT The purpose of the U.S. Department of Transportation’s (DOT) drug and alcohol program is to protect the safety of employees, co-workers, and the traveling public. However, drug testing for transportation employees does not determine impairment for over-the-counter and prescribed medications. A covered employee under the influence of over-the-counter and prescription medications poses the same threat to safety as one who is under the influence of illicit drugs; therefore, measures should be taken to deter any impairing substance – regardless of whether or not the substance is legally obtained. Some over-the-counter and prescription medications have the potential to cause impairment; however, it is difficult to determine the dosage levels at which one will become impaired. Urine collection is the means of collection and is susceptible to subversion attempts. More research is needed to determine the method of collection and the dose at which one becomes impaired. The Occupational and Environmental Health Nurse (OHN) is uniquely qualified to manage drug and alcohol programs due to experience in clinical nurse training and comprehensive workplace knowledge. The OHN recognizes the physical and psychological symptoms of drug impairment and can assist with employee assistance program referrals as needed.
    [Show full text]
  • Final Name 2020 Annual Meeting Program
    ANNUAL MEETING OCTOBER 16-17, 2020 <Virtual Conference> NAME 2020 Annual Meeting Cyberspace, Everywhere Table of Contents Welcome to Annual Meeting .............................................................................................................................. NAME Officers and Board of Directors ............................................................................................................... NAME Committees ............................................................................................................................................. CME Information ................................................................................................................................................ Meeting Program ................................................................................................................................................ Exhibits: Exhibit Schedule ................................................................................................................................................ Participating Exhibitor Descriptions .................................................................................................................... Optional/Special Programs: Inspection and Accreditation: Inspector Training Course ................................................................................... NAME Foundation Outreach Fundraiser, “Drug Delivery Homicide: The Straw that Breaks the Camel’s Back” ................................................................
    [Show full text]
  • Services and Capabilities Deep Dive: Substance Use Disorders Download
    DEEP DIVE A DEEPER DIVE INTO SUBSTANCE ABUSE DISORDERS AN INTEGRATED ADVANTAGE As a full-service and therapeutically-focused CRO, Medpace specializes in the design and conduct of global trials in substance use disorders clinical research, including psychiatry. We bring a global footprint, strategic medical, regulatory, and operational leadership as well as fully integrated Central Labs and Core Imaging services to accelerate substance use disorder studies. • Highly relevant operational know-how and subject matter expertise in managing and executing substance use disorder studies • A well-profiled network of investigative sites enables timely enrollment and high-quality conduct of trials • End-to-end suite of global imaging services seamlessly integrated into the overall structure of the trial • A wide range of relevant biomarker assays through our wholly-owned central and bioanalytical lab network THERAPEUTICALLY-FOCUSED TEAM Medpace is unique in its scientifically-driven approach to clinical research. Our model gives Sponsors the advantage of early and ongoing insight and guidance from a team of therapeutic experts throughout the trial design and execution. Our highly experienced team of medical, regulatory, and operational experts work collaboratively to conduct clinical trials. We understand issues from the perspectives of Sponsors, clinical investigators, scientific leaders, and reviewers at regulatory agencies. With this insight, we successfully define and execute clear development plans from beginning to end. NEUROSCIENCE Page 1 of 6 EXPERTS Sarah DeRossett, MD, PhD Senior Medical Director, Medical Department, Neurology, Psychopharmacology, Analgesia EXPERT INSIGHT Dr. Sarah DeRossett is a board-certified neurologist Serving as therapeutic team leaders, our in-house with 15 years of experience in clinical and academic medical doctors apply years of psychiatric/neurologic neurology, plus more than 10 years of drug drug development experience to each study.
    [Show full text]
  • LAW ENFORCEMENT TRAINING ACADEMY Student Handbook Program Addendum
    LAW ENFORCEMENT TRAINING ACADEMY Student Handbook Program Addendum 518 W. Prospect St. Smithville, OH 44677 Phone: 330.669.7070 Fax: 330.669.7071 http://www.wcscc.org/adulted/ Updated August 2020 Law Enforcement Training Academy Student handbook program addendum Rules and Regulations for Police Cadets of the WCSCC Law Enforcement Training Academy Academy Commander: Chief Ryan Pearson Public Safety Coordinator: Gregory Chandler Adult Education Manager: Sandy Elliott Director of Operations & Adult Education: Lynn Moomaw ACKNOWLEDGMENT OF RECEIPT As a police Cadet, it is your duty to thoroughly familiarize yourself and comply with this handbook and with all official directives and rules. The Student Handbook has been written to maximize training and instill in cadets the requisite desired traits of a Law Enforcement Officer. The public trust of law enforcement is built over time through demonstrated professionalism and integrity; yet, it can be shattered with a single, thoughtless act of an officer or civilian employee. The public expects law enforcement officers to behave in an exemplary manner at all times. The Academy Staff expects exceptional adherence to our values and ethical standards at all times. The Academy is designed to instill this in cadets long before they encounter the public. Any cadet who, through their off duty behavior, brings discredit to the WCSCC and the Academy shall be subject to discipline or termination. A standard of objective reasonableness will be used to determine an occurrence of questionable behavior. I ACKNOWLEDGE RECEIPT OF THE STUDENT HANDBOOK AND ADDENDUM. I UNDERSTAND THAT ALL POLICIES, PROCEDURES, RULES OR REGULATIONS, AND STANDARDS CONTAINED IN THIS HANDBOOK APPLY TO ME UNTIL I AM GRADUATED FROM THE PROGRAM.
    [Show full text]
  • Direct Analysis of Urinary Opioids and Metabolites by Mixed-Mode Μelution SPE Combined with UPLC/MS/MS for Clinical Research by Jonathan P
    21 Direct Analysis of Urinary Opioids and Metabolites by Mixed-mode µElution SPE Combined with UPLC/MS/MS for Clinical Research by Jonathan P. Danaceau, Erin E. Chambers, and Kenneth J. Fountain, Waters Corporation, Milford, MA The analysis of natural and synthetic opioid drugs continues to be an important aspect of clinical research. In the past, analyses were typically conducted by GC/MS after first subjecting the samples to acid or enzymatic hydrolysis to transform the glucuronide metabolites into the parent form [1]. With the advent of modern LC/MS/MS techniques, however, glucuronide metabolites can now be analysed directly [2-5]. Direct analyses of glucuronide metabolites can eliminate the risk of inaccurate quantification due to incomplete hydrolysis, as enzymatic efficiency can vary greatly depending upon the enzyme used and the drug substrate analysed [6]. The sample preparation approach is also an TX). Complementary, deuterated internal Table 1: UPLC solvent gradient important consideration. Urine samples, standards were used for all compounds with unlike some other matrices, can be analysed the exception of hydromorphone-3- Time (min.) Flow Rate %A %B by ‘dilute and shoot’ methods in which glucuronide, codeine-6-glucuronide, samples are diluted with an internal standard norbuprenorphine-glucuronide, norfentanyl, 0 0.4 98.0 2.0 mix and directly injected onto a LC/MS/MS and buprenorphine-glucuronide. For these 6 0.4 47.2 52.8 system [2, 4]. Disadvantages to this type of compounds, a deuterated IS with the most technique, however, include the fact that similar recovery and matrix effect was chosen 6.5 0.4 98.0 2.0 urine contains many matrix components that as a surrogate.
    [Show full text]