Tandem mass spectrometry techniques for the TDM of antifungals : new perspectives and challenges
|
|
- Roxanne Preston
- 6 years ago
- Views:
Transcription
1 Tandem mass spectrometry techniques for the TDM of antifungals : new perspectives and challenges 1 st International Workshop on Clinical Pharmacology of Antifungal Drugs and Fungal Diseases Berlin, April 26, 2013 Dr Laurent Decosterd, PhD Innovation & Development Unit, Laboratory of Clinical Pharmacology, Service of Biomedicine, CHUV Lausanne
2 Therapeutic Drug Monitoring (TDM) Rationale and usefulness of TDM Principle of Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) Multiplex analysis of antifungal drugs Selected examples of applications Monitoring of antifungal drugs combination Identification of altered metabolism of voriconazole Detection of previous treatments Conclusions
3 Therapeutig Drug Monitoring (TDM) : Measurement of plasma concentration under treatment Dosage individualization based on plasma levels, targeting a pre-defined range Better chances of achieving therapeutic efficacy Reduced risks of meeting toxicity Candidate Drugs : Therapeutic Drug Monitoring (TDM) General principles Drugs administrated on the long-term (chronic conditions) Drugs administrated to critically ill patients, with limited remaining therapeutic options (ICU). Significant inter-patient pharmacokinetic variability Low intra-patient pharmacokinetic variability Consistent concentration - efficacy / toxicity relationships
4 Therapeutic Drug Monitoring (TDM) Should be considered in case of lack of early, or easily accessible pharmacodynamic surrogates Unexpected clinical toxicities Less than expected clinical response Drug-drug or drug-food interactions Changes in patho-physiological state, that may impair gastrointestinal, hepatic or renal function Pregnancy and pediatric patients Monitoring short-term adherence
5 Therapeutic Drug Monitoring (TDM) Antifungal drugs meet the overall criteria for the implementation of a routine TDM program Measurements and interpretations!!! Reliable analytical methods must be available
6 Development of UPLC-tandem MS method for the assay of antifungals drugs Results must be available for TDM interpretations within 24-48h hours The analytical method must be: Rapid (and user-friendly) Precise (to limit the number of replicates) Accurate (obviously )
7 Instrument of High or Ultra Performance Liquid Chromatography (HPLC, UPLC ) High pressure pump ( bar) Auto-sampler (samples) Chromatography column (drugs and metabolites separation) Detector: UV, fluorescence electrochemical MS, MS/MS ml/min Solvents (MeCN, MeOH, H 2 O) Data processing (PC)
8 Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) From HPLC column The Ionisation Step To the first quadrupole of the MS instrument
9 Selection of parent ion: (i.e. molecular mass : m/z (fluconazole) Selection of product ion (for instance: caracteristic fragment: m/z 238 daughter mass for fluconazole) N N N OH + N N OH N N F N N F F F We observe (and actually measure) The transition m/z [M+H + ] m/z 238
10 (Triple Stage Quadripole Mass Spectrometer) TSQ Quantum, Thermo Scientific Corporation
11 Strength and Limitations of Tandem Mass Spectrometry Ionisation From HPLC column To the first quadrupole of the MS instrument Strength: ultimate selectivity (thanks to triple quadripole mass detection) Limitations: Ionisation of the analyte may be influenced by the presence of endogenous matrix components co-eluting with the target analyte that may influence its ionisation: = the so-called MATRIX EFFECT (Achilles' heel) This influence must be eliminated or at least normalised.
12 Stable isotope-labeled internal Standards (I.S.) and IS calibration method Ionisation step From HPLC column To the first quadrupole of the MS instrument The use of stable isotope-labeled internal standards is the first choice approach to minimize the influence of matrix effect due to endogenous components co-eluting with the analytes that affects signal intensity, and hence, the accuracy and precision of a quantitative method. Of particular importance when using electrospray ionisation mass spectrometry. The potential influence of can be normalised using the corresponding stable isotope-labeled Internal Standards (deuterium, 13 C).
13 «Multiplex» Analyses of antifungal drugs Fluconazole Voriconazole Voriconazole-N-oxide Posaconazole Itraconazole Hydroxy-itraconazole Caspofungine Anidulafungine Hydroxy-itraconazole Posaconazole Antimicrob Agents Chemother, 54, (2010)
14 «Multiplex» assay: Analysis of drugs from the same therapeutic class in a single chromatographic run Advantages : Unique sample extraction procedure and short analytical run. Saves times by the establishment of simultaneous calibration curves Applicable for blood samples from patients receiving either different single-drug, or combination regimens Results obtained on a daily basis: TDM dosing adjustments performed within shortest time intervals. Detection of other drugs possibly present in sample.
15 An Ultra-Performance Liquid Chromatography - tandem MS method for the simultaneous determination of 6 antifungal agents and their metabolites Fluconazole Posaconazole Fluconazole-d4 Posaconazole-d4 Voriconazole-NO HO-itraconazole Voriconazole-NO-d3 HO-itraconazole-d5 Voriconazole Anidulafungin Voriconazole-d3 Caspofungin Itraconazole Caspofungin analogue Itraconazole-d5 The chromatographic separation of 8 compounds takes place in less than 5 minutes
16 Voriconazole N-oxide : in source metabolite dissociation voriconazole 2.7 µg/ml Chromatogram from an Acute Lymphoblastic Leukemia ( ALL) patient on oral voriconazole 400 mg BID. 0.4 µg/ml Voriconazole trough level was 0.4 µg/ml (below the proposed therapeutic range) Voriconazole N-oxide level was 2.7 µg/ml suggesting an accelerated hepatic metabolism with first pass effect on oral bioavailability Importance of the chromatographic separation to avoid cross-talk!
17 MULTIPLEX ASSAY 1. Monitoring of antifungals drugs combination 2. Detection of previous treatment Fluconazole stopped 50 days before sampling 0.5 µg/ml 0.16 µg/ml 3.0 µg/ml 1.9 µg/ml 2.6 µg/ml 1.0 µg/ml Antimicrob Agents Chemother, 54, (2010)
18 The simultaneous assay of voriconazole and voriconazole-no is an index of the phenotyping activity of CYP2C19, that integrates : genetic background, liver function, and drugs interactions Hyland, R., B. C. Jones, and D. A. Smith Identification of the cytochromep450 enzymes involved in the N-oxidation of voriconazole. Drug Metab. Dispos. 31:
19 MULTIPLEX ASSAY 3. High voriconazole levels with impaired liver metabolism 4. Increased voriconazole metabolism as evidenced by High voriconazole-no levels C:\Xcalibur\...\Fong-b205\fong-b205_018 2/27/2013 5:13:00 PM P 6676 RT: SM: 15B Relative Abundance RT: 2.48 AA: RT: 2.93 AA: RT: 2.93 AA: NL: 3.12E5 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b205_018 Voriconazole-NO NL: 1.54E6 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b205_018 Voriconazole 7.2 µg/ml NL: 2.90E6 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b205_018 C:\Xcalibur\...\Fong-b220\fong-b220c_020 4/15/2013 8:36:52 PM P 6894 RT: SM: 15B Relative Abundance RT: 2.20 AA: µg/ml µg/ml RT: 2.66 AA: RT: 2.65 AA: Voriconazole-NO Voriconazole 2.0 µg/ml NL: 2.56E6 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b220c_020 NL: 2.97E5 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b220c_020 NL: 2.57E6 TIC F: + c ESI SRM ms [ ] MS ICIS fong-b220c_ Voriconazole-d Voriconazole-d Time (min) Time (min)
20 How accurate is the multiplex assay? External Quality Control Program KKGT, Stichting Kwaliteitsbewaking Klinische Geneesmiddelanalyse en Toxicologie: Association for Quality Assessment in TDM and clinical Toxicology, The Hague, The Netherlands. International Interlaboratory External Quality Assurance Program for antifungals agents (organized at present for azoles and flucytosine)
21 International Interlaboratory External Quality Assurance Program for antifungals agents (57 labos): LAUSANNE CHUV Results for 2012
22
23 Probability of response to voriconazole (solid line) and of grade 3 neurotoxicity (dashed line) as a function of voriconazole trough plasma concentrations in adult patients with invasive fungal infections Pascual A, Csajka C et al & Marchetti O, Clin Infect Dis 2012 Therapeutic range : 1.5 to 4.5 mg/l
24 «Multiplex» assay: LIMITATIONS Restricted to analytes contained in the calibration samples. Total number of drugs in calibration is not infinite, because of solubility issues of drugs in the matrix-match calibration samples, especially for lipophilic drugs at high concentrations (requiring the addition of nonmatrix components (i.e. solvents) : < 10% of total biological matrix volume of calibrators. Calibration curves established for each analytical series, but used only in case of patients samples. Possibly requires an additional step of validation. i.e. cross-validation calibration: «single analyte» versus «multiplex» analysis. Important in case of co-elution of analytes to exclude the occurence of reciprocal competition at the ionisation step. Easily circumvented, if stable isotopically labelled (D, 13 C,) Internal Standards of drugs are available.
25 LC tandem MS assay of further antifungal drugs Isavuconazole Micafungin Amphotericin B (free and total levels and liposomal fraction) New antifungal agents of current and future classes
26 Tandem mass spectrometry techniques for the TDM of antifungals: challenges Availability to isotopically labelled (D, 13 C) Internal Standards (IS) for echinocandins (and new antifungal agents is the future) is a recurring issues. Efforts for a facilitated access must be prioritized. The assay of amphotericin B (administered as liposomal formulation) is an additional analytical challenge. Total amphotericin B plasma levels (free + liposomal) (ie. after liposomal disruption with suitable methodology (i.e. detergent, sonication)) Free plasma levels of amphotericin B
27 TDM of antifungals: Conclusions The concentration of antifungal drug measured in plasma is at present the best marker of exposure in patient, integrating both genetic and non-genetic (drug interactions, patients pathophysiology, etc) influences. Strong arguments exist for implementing TDM for antifungal drugs, based on patients plasma concentrations. Randomised trials of prospective TDM intervention integrating clinical outcome, emergence of resistance and morbidity/mortality are still lacking. In the emerging field of Personalized Medicine, the development of TDM for patient-tailored dosage adjustment of antifungal therapy should allow to maximize both the therapeutic benefit and the tolerability of drugs. The right dose of the right drug to the right patient.
28 Acknowlegments Laboratory Thomas Mercier Dr Boris Zanolari Beatrice Ternon Sandra Cruchon Nicole Guignard Research Scientists Manel Aouri, PhD student Jaurès Blanc, PhD student Dr Aurélie Fayet Mello Dr Nicolas Widmer Partners within the Lausanne University Hospital Prof Oscar Marchetti Prof Chantal Csajka Prof Thierry Buclin PD Dr Matthias Cavassini Prof Amalio Telenti Prof Chin Bin Eap
29 Financial Supports and Collaborations Centre Coordonné d Oncologie ambulatoire, CCO Lausanne Swiss Tropical Institute Basel
Received 25 March 2010/Returned for modification 21 June 2010/Accepted 28 August 2010
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2010, p. 5303 5315 Vol. 54, No. 12 0066-4804/10/$12.00 doi:10.1128/aac.00404-10 Copyright 2010, American Society for Microbiology. All Rights Reserved. Multiplex
More informationUPLC-MS/MS Analysis of Azole Antifungals in Serum for Clinical Research
Stephen Balloch and Gareth Hammond Waters Corporation, Wilmslow, UK APPLICATION BENEFITS Analytical selectivity afforded by mass selective detection Wide linear measuring range Simple, inexpensive sample
More informationSample Concentration and Analysis of Human Hormones in Drinking Water
Sample Concentration and Analysis of Human Hormones in Drinking Water Carl Fisher Applications Chemist Ion Chromatography/Sample Preparation Thermo Fisher Scientific March 1, 215 1 The world leader in
More informationHigh-Throughput, Cost-Efficient LC-MS/MS Forensic Method for Measuring Buprenorphine and Norbuprenorphine in Urine
High-Throughput, Cost-Efficient LC-MS/MS Forensic Method for Measuring and in Urine Xiaolei Xie, Joe DiBussolo, Marta Kozak; Thermo Fisher Scientific, San Jose, CA Application Note 627 Key Words, norbuprenorphine,
More informationQuantitative Analysis of THC and Main Metabolites in Whole Blood Using Tandem Mass Spectrometry and Automated Online Sample Preparation
Quantitative Analysis of THC and Main Metabolites in Whole Blood Using Tandem Mass Spectrometry and Automated Online Sample Preparation Valérie Thibert, Bénédicte Duretz Thermo Fisher Scientific, Courtaboeuf,
More informationDevelopment of a Bioanalytical Method for Quantification of Amyloid Beta Peptides in Cerebrospinal Fluid
Development of a Bioanalytical Method for Quantification of Amyloid Beta Peptides in Cerebrospinal Fluid Joanne ( 乔安妮 ) Mather Senior Scientist Waters Corporation Data courtesy of Erin Chambers and Mary
More informationQuantitative Analysis of Vit D Metabolites in Human Plasma using Exactive System
Quantitative Analysis of Vit D Metabolites in Human Plasma using Exactive System Marta Kozak Clinical Research Applications Group Thermo Fisher Scientific San Jose CA Clinical Research use only, Not for
More informationMeasuring Lipid Composition LC-MS/MS
Project: Measuring Lipid Composition LC-MS/MS Verification of expected lipid composition in nanomedical controlled release systems by liquid chromatography tandem mass spectrometry AUTHORED BY: DATE: Sven
More informationReal-time PK Measurement of the Chemotherapeutic Drug Melphalan in Whole Blood by a Novel PaperSpray Mass Spectrometry
Palm Springs, California February 21-25 Real-time PK Measurement of the Chemotherapeutic Drug Melphalan in Whole Blood by a Novel PaperSpray Mass Spectrometry Junfang Zhao, Chandra Sharat, Parinda A. Mehta,
More informationRobust and Fast Analysis of Tobacco-Specific Nitrosamines by LC-MS/MS
Application Note 242 Robust and Fast Analysis of Tobacco-Specific Nitrosamines by LC-MS/MS INTRODUCTION Tobacco-specific nitrosamines (TSNA) are a group of carcinogens found only in tobacco products. They
More informationHigh-Throughput Quantitative LC-MS/MS Analysis of 6 Opiates and 14 Benzodiazepines in Urine
High-Throughput Quantitative LC-MS/MS Analysis of and 14 Benzodiazepines in Urine Bill Yu, Kristine Van Natta, Marta Kozak, Thermo Fisher Scientific, San Jose, CA Application Note 588 Key Words Opiates,
More informationDETERMINATION OF CANNABINOIDS, THC AND THC-COOH, IN ORAL FLUID USING AN AGILENT 6490 TRIPLE QUADRUPOLE LC/MS
FORENSICS AND TOXICOLOGY ANALYSIS DETERMINATION OF CANNABINOIDS, THC AND THC-COOH, IN ORAL FLUID USING AN AGILENT 6490 TRIPLE QUADRUPOLE LC/MS Solutions for Your Analytical Business Markets and Applications
More informationDetection of Cotinine and 3- hydroxycotine in Smokers Urine
Detection of Cotinine and 3- hydroxycotine in Smokers Urine Behavioural and Situational Research Group School of Medicine, University of Tasmania Version number: 2 Effective date: 01/12/2015 Review due:
More informationA Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum
A Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum Yi Xiao, 1 Yan-Kang Xu, 1 Paul Pattengale, 1,2 Maurice
More informationDr. Erin E. Chambers Waters Corporation. Presented by Dr. Diego Rodriguez Cabaleiro Waters Europe Waters Corporation 1
Development of an SPE-LC/MS/MS Assay for the Simultaneous Quantification of Amyloid Beta Peptides in Cerebrospinal Fluid in Support of Alzheimer s Research Dr. Erin E. Chambers Waters Corporation Presented
More informationO O H. Robert S. Plumb and Paul D. Rainville Waters Corporation, Milford, MA, U.S. INTRODUCTION EXPERIMENTAL. LC /MS conditions
Simplifying Qual/Quan Analysis in Discovery DMPK using UPLC and Xevo TQ MS Robert S. Plumb and Paul D. Rainville Waters Corporation, Milford, MA, U.S. INTRODUCTION The determination of the drug metabolism
More informationThe Comparison of High Resolution MS with Triple Quadrupole MS for the Analysis of Oligonucleotides
The Comparison of High Resolution MS with Triple Quadrupole MS for the Analysis of Oligonucleotides Mohammed Abrar Unilabs York Bioanalytical Solutions Outline Introduction Why LC-MS/MS? Limitations of
More informationSummary Chapter 8 CHAPTER 8. Summary. Page 173
CHAPTER 8 Summary Page 173 Chapter 2: Liquid Chromatography/Tandem Mass Spectrometry Method for Quantitative Estimation of PEG 400 and its Applications A rapid sensitive and selective MRM based method
More informationTherapeutic Drug Monitoring in Antifungal Therapy. Why, When and How
Therapeutic Drug Monitoring in Antifungal Therapy Why, When and How Roger Brüggemann Radboud University Nijmegen Medical Centre and Nijmegen Institute for Infection, Inflammation and Immunology (N4i) Trends
More informationCONTENT. i iv ix. SVKM s NMIMS, School of Pharmacy and Technology Management
CONTENT Chapter No. Title Page No. Abbreviations List of Figures List of Tables 1 Introduction 1 1.1 Practical aspects 4 1.2 Stability-indicating assay method (SIAM) 5 1.3 Regulatory aspects 6 1.4 Techniques
More informationRobust extraction, separation, and quantitation of structural isomer steroids from human plasma by SPE-UHPLC-MS/MS
TECHNICAL NOTE 21882 Robust extraction, separation, and quantitation of structural isomer steroids human plasma by SPE-UHPLC-MS/MS Authors Jon Bardsley 1, Kean Woodmansey 1, and Stacy Tremintin 2 1 Thermo
More informationI am against to TDM in critically ill patient
TDM I am against to TDM in critically ill patient TDM of antifungals: where are we? Dr. Rafael Zaragoza Antifungal therapy in ICU; prophylaxis, pre-emptive and targeted Conflicts of interest: Pfizer Astellas
More informationRapid, Simple Impurity Characterization with the Xevo TQ Mass Spectrometer
Robert Plumb, Michael D. Jones, and Marian Twohig Waters Corporation, Milford, MA, USA INTRODUCTION The detection and characterization of impurities and degradation products of an active pharmaceutical
More informationLC-MS/MS Method for the Determination of Raloxifene and its Glucuronide Metabolites from Human Plasma Using SPE Micro Elution
LC-MS/MS Method for the Determination of Raloxifene and its Glucuronide Metabolites from Human Plasma Using SPE Micro Elution Krishna Rao Dara, Dr. Tushar N. Mehta, Centre of Excellence for Asia Pacific
More informationUPLC/MS Monitoring of Water-Soluble Vitamin Bs in Cell Culture Media in Minutes
UPLC/MS Monitoring of Water-Soluble Vitamin Bs in Cell Culture Media in Minutes Catalin E. Doneanu, Weibin Chen, and Jeffrey R. Mazzeo Waters Corporation, Milford, MA, U.S. A P P L I C AT ION B E N E F
More informationApplication Note LCMS-108 Quantitation of benzodiazepines and Z-drugs in serum with the EVOQ TM LC triple quadrupole mass spectrometer
Application Note LCMS-108 Quantitation of benzodiazepines and Z-drugs in serum with the EVOQ TM LC triple quadrupole mass spectrometer Abstract This study demonstrates a sensitive, rapid and reliable research
More informationMS/MS as an LC Detector for the Screening of Drugs and Their Metabolites in Race Horse Urine
Application Note: 346 MS/MS as an LC Detector for the Screening of Drugs and Their Metabolites in Race Horse Urine Gargi Choudhary and Diane Cho, Thermo Fisher Scientific, San Jose, CA Wayne Skinner and
More informationSPE-LC-MS/MS Method for the Determination of Nicotine, Cotinine, and Trans-3-hydroxycotinine in Urine
SPE-LC-MS/MS Method for the Determination of Nicotine, Cotinine, and Trans-3-hydroxycotinine in Urine J. Jones, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 709 Key Words SPE, SOLA
More informationUltra Performance Liquid Chromatography Coupled to Orthogonal Quadrupole TOF MS(MS) for Metabolite Identification
22 SEPARATION SCIENCE REDEFINED MAY 2005 Ultra Performance Liquid Chromatography Coupled to Orthogonal Quadrupole TOF MS(MS) for Metabolite Identification In the drug discovery process the detection and
More informationESCMID Online Lecture Library. by author. Salvage Therapy of Invasive Aspergillosis Refractory to Primary Treatment with Voriconazole
Salvage Therapy of Invasive Aspergillosis Refractory to Primary Treatment with Voriconazole J.A. Maertens, hematologist, MD, PhD University Hospital Gasthuisberg Leuven, Belgium Current guidelines: first-line
More informationNeosolaniol. [Methods listed in the Feed Analysis Standards]
Neosolaniol [Methods listed in the Feed Analysis Standards] 1 Simultaneous analysis of mycotoxins by liquid chromatography/ tandem mass spectrometry [Feed Analysis Standards, Chapter 5, Section 1 9.1 ]
More informationA Novel Solution for Vitamin K₁ and K₂ Analysis in Human Plasma by LC-MS/MS
A Novel Solution for Vitamin K₁ and K₂ Analysis in Human Plasma by LC-MS/MS By Shun-Hsin Liang and Frances Carroll Abstract Vitamin K₁ and K₂ analysis is typically complex and time-consuming because these
More informationDetermination of Clarithromycin in Human Plasma by LC-EI Tandem Mass Spectrometry: Application to Bioequivalence Study
Determination of Clarithromycin in Human Plasma by LC-EI Tandem Mass Spectrometry: Application to Bioequivalence Study Syed N Alvi, Ph.D Clinical Studies & Empirical Ethics Department King Faisal Specialist
More informationJoin the mass movement towards mass spectrometry
Join the mass movement towards mass spectrometry Thermo Scientific ISQ EC single quadrupole mass spectrometer Embrace the power of mass spectrometry Achieving a comprehensive understanding of the samples
More informationOptimizing antifungal dosing regimens. Joseph Meletiadis, PhD, FECMM Assistant Professor of Microbiology
ATHENA 2017 International Conference November 28 30, 2017 Optimizing antifungal dosing regimens Joseph Meletiadis, PhD, FECMM Assistant Professor of Microbiology Clinical Microbiology Laboratory, «Attikon»
More informationDry eye disease commonly known as atopic keratoconjunctivitis is an autoimmune disease of
4.1. Introduction Dry eye disease commonly known as atopic keratoconjunctivitis is an autoimmune disease of eyes. The disease is characterized by lesser or some time no-significant production of tear;
More informationLC-MS/MS quantitative analysis of Polyunsaturated Omega 3, 6,7 and 9 Fatty Acids in Serum for
POSTER NOTE 64921 LC-MS/MS quantitative analysis of Polyunsaturated Omega 3, 6,7 and 9 Fatty Acids in Serum for Research Use LC-MS/MS quantitative analysis of Poly Rory M Doyle*, Thermo Scientific, Inc,
More informationComprehensive Two-Dimensional HPLC and Informative Data Processing for Pharmaceuticals and Lipids
PO-CON1576E Comprehensive Two-Dimensional HPLC and Informative Data Processing for Pharmaceuticals and Lipids HPLC 2015 PSB-MULTI-06 Yoshiyuki WATABE, Tetsuo IIDA, Daisuke NAKAYAMA, Kanya TSUJII, Saki
More informationMaria João Mendes Mendonça Barreira Department of Health Promotion and Chronic Deseases, INSA
Quantification of four immunosuppressant drugs by Liquid Chomatography-Tandem Mass Spectrometry using Direct Injection. Maria João Mendes Mendonça Barreira Department of Health Promotion and Chronic Deseases,
More informationDetermination of Amantadine Residues in Chicken by LCMS-8040
Liquid Chromatography Mass Spectrometry Determination of Amantadine Residues in Chicken by LCMS-8040 A method for the determination of amantadine in chicken was established using Shimadzu Triple Quadrupole
More informationExtraction of Synthetic and Naturally Occurring Cannabinoids in Urine Using SPE and LC-MS/MS
Extraction of Synthetic and Naturally Occurring Cannabinoids in Urine Using SPE and LC-MS/MS UCT Part Numbers SSHLD063 Styre Screen HLD 60 mg, 6 ml column SPHPHO6001-5 Select ph Buffer Pouches 100 mm Phosphate
More informationGradient Elution LC-MS/MS Determination of Gefitinib in Rat Plasma and its Pharmacokinetic Study
Latin American Journal of Pharmacy (formerly Acta Farmacéutica Bonaerense) Lat. Am. J. Pharm. 32 (2): 292-6 (2013) Short Communication Received: November 20, 2012 Accepted: December 6, 2012 Gradient Elution
More informationQuadrupole and Ion Trap Mass Analysers and an introduction to Resolution
Quadrupole and Ion Trap Mass Analysers and an introduction to Resolution A simple definition of a Mass Spectrometer A Mass Spectrometer is an analytical instrument that can separate charged molecules according
More informationPharmacologyonline 1: (2010) Newsletter Mohan et al.
SIMPLE AND ROBUST METHOD FOR THE QUANTIFICATION OF LEVONORGESTREL IN PLASMA BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ELECTROSPRAY IONIZATION MASS SPECTROMETRY Reddy C.Mohan 1, Gajjar A.K 2 and Khan A.Hussian
More informationEvaluation of an LC-MS/MS Research Method for the Analysis of 33 Benzodiazepines and their Metabolites
Evaluation of an LC-MS/MS Research Method for the Analysis of 33 Benzodiazepines and their Metabolites Valérie Thibert 1, Norbert Dirsch 2, Johannes Engl 2, Martin Knirsch 2 1 Thermo Fisher Scientific,
More informationSEPARATION OF BRANCHED PFOS ISOMERS BY UPLC WITH MS/MS DETECTION
SEPARATION OF BRANCHED PFOS ISOMERS BY UPLC WITH MS/MS DETECTION Marian Twohig 1, Nicholas Ellor 1, Keith Worrall 2, Tim Jenkins 2, Gordon Kearney 2 1 Waters Corporation, 1 Cummings Center, Beverly, MA
More informationOffline and online sample extraction for the quantification of benzodiazepines in human plasma or serum for clinical research
TECHNICAL NOTE 64913 Valium (diazepam) structure Offline and online sample extraction for the quantification of benzodiazepines in human plasma or serum for clinical research Authors Claudio De Nardi,
More informationBioanalytical Quantitation of Biotherapeutics Using Intact Protein vs. Proteolytic Peptides by LC-HR/AM on a Q Exactive MS
Bioanalytical Quantitation of Biotherapeutics Using Intact Protein vs. Proteolytic Peptides by LC-HR/AM on a Q Exactive MS Jenny Chen, Hongxia Wang, Zhiqi Hao, Patrick Bennett, and Greg Kilby Thermo Fisher
More informationAnalysis of Limonin in Citrus Juice Using QuEChERS and LC-MS/MS
Analysis of Limonin in Citrus Juice Using QuEChERS and LC-MS/MS UCT Part Numbers ECQUEU7-MP Mylar pouch containing 4g MgSO4, 1g NaCl, 1g Na3Cit 2H2O and 0.5g Na2Cit 1.5H2O CUMPSC1875CB2CT 2mL dspe tube
More informationSimple Method (IS-MRM) to Monitor Lysophospholipids and Phospholipids During LC-MS Method Development via In-Source CID
Simple Method (IS-MRM) to Monitor Lysophospholipids and Phospholipids During LC-MS Method Development via In-Source CID James Little, Eastman Chemical Company, Kingsport, TN Overview Phospholipids and
More informationAutomated Purification and Analytical Reinjection of a Small Molecule Drug, Probenecid, on a Gilson LC/MS Dual Function System
Automated Purification and Analytical Reinjection of a Small Molecule Drug, Probenecid, on a Gilson LC/MS Dual Function System Keywords Introduction Application Note PHA0413 High Pressure Liquid Chromatography
More informationDienes Derivatization MaxSpec Kit
Dienes Derivatization MaxSpec Kit Item No. 601510 www.caymanchem.com Customer Service 800.364.9897 Technical Support 888.526.5351 1180 E. Ellsworth Rd Ann Arbor, MI USA TABLE OF CONTENTS GENERAL INFORMATION
More informationShotgun Proteomics MS/MS. Protein Mixture. proteolysis. Peptide Mixture. Time. Abundance. Abundance. m/z. Abundance. m/z 2. Abundance.
Abundance Abundance Abundance Abundance Abundance Shotgun Proteomics Protein Mixture 1 2 3 MS/MS proteolysis m/z 2 3 Time µlc m/z MS 1 m/z Peptide Mixture m/z Block Diagram of a Mass Spectrometer Sample
More informationApplying a Novel Glycan Tagging Reagent, RapiFluor-MS, and an Integrated UPLC-FLR/QTof MS System for Low Abundant N-Glycan Analysis
Applying a Novel Glycan Tagging Reagent, RapiFluor-MS, and an Integrated UPLC-FLR/QTof MS System for Low Abundant N-Glycan Analysis Ying Qing Yu Waters Corporation, Milford, MA, USA APPLICATION BENEFITS
More informationIdentification & Confirmation of Structurally Related Degradation Products of Simvastatin
Identification & Confirmation of Structurally Related Degradation Products of Simvastatin Power of QTRAP Systems for Identification and Confirmation of Degradation Products Dilip Reddy 1, Chandra Sekar
More informationGlycerolipid Analysis. LC/MS/MS Analytical Services
Glycerolipid Analysis LC/MS/MS Analytical Services Molecular Characterization and Quantitation of Glycerophospholipids in Commercial Lecithins by High Performance Liquid Chromatography with Mass Spectrometric
More informationMonitorization, Separation and Quantification of Antifungals used for Invasive Aspergillosis Treatment by High Performance Thin Layer Chromatography
Monitorization, Separation and Quantification of Antifungals used for Invasive Aspergillosis Treatment by High Performance Thin Layer Chromatography M. P. Domingo, M. Vidal, J. Pardo, A. Rezusta, L. Roc,
More informationMethods in Mass Spectrometry. Dr. Noam Tal Laboratory of Mass Spectrometry School of Chemistry, Tel Aviv University
Methods in Mass Spectrometry Dr. Noam Tal Laboratory of Mass Spectrometry School of Chemistry, Tel Aviv University Sample Engineering Chemistry Biology Life Science Medicine Industry IDF / Police Sample
More informationTherapeutic Drug Monitoring
Therapeutic Drug Monitoring news from the laboratory Pieter Vermeersch, Steven Pauwels, Matthijs Oyaert Laboratory Medicine, UZ Leuven Overview 1. Introduction 2. Analytical methods 3. Testing on dry blood
More informationIdentification and Quantification of Psychedelic Phenethylamine 2C Series using SPE and LC-MS/MS
Identification and Quantification of Psychedelic Phenethylamine 2C Series using SPE and LC-MS/MS UCT Part Numbers: CSXCE106-Clean Screen XCEL I 130mg/6mL SLDA100ID21-3UM - Selectra DA HPLC column, 100
More informationAntifungal Pharmacodynamics A Strategy to Optimize Efficacy
Antifungal Pharmacodynamics A Strategy to Optimize Efficacy David Andes, MD Associate Professor, Department of Medicine Division of Infectious Diseases Medical Microbiology and Immunology University of
More informationDetermination of cyclovirobuxine D in human plasma by liquid chromatography tandem mass spectrometry and application in a pharmacokinetic study
Acta Pharmaceutica Sinica B 2011;1(3):184 188 Institute of Materia Medica, Chinese Academy of Medical Sciences Chinese Pharmaceutical Association Acta Pharmaceutica Sinica B www.elsevier.com/locate/apsb
More informationVitamin D3 and related compounds by ESI and APCI
Liquid Chromatography Mass Spectrometry SSI-LCMS-9 Vitamin D and related compounds by ESI and APCI LCMS-8 Summary Vitamin D and related compounds were measured by LC-ESI/APCI-MS-MS. Background Accurate
More informationTandem mass spectrometry analysis of prostaglandins and isoprostanes
Tandem mass spectrometry analysis of prostaglandins and isoprostanes Jeevan Prasain jprasain@uab.edu 6-2612 verview Introduction to PGs and their synthesis Mass spectrometry characterization of PGs and
More informationSUPPORTING INFORMATION FOR: CONCENTRATIONS OF POLYBROMINATED DIPHENYL ETHERS, HEXABROMOCYCLODODECANES AND TETRABROMOBISPHENOL-A IN BREAST MILK FROM
SUPPORTING INFORMATION FOR: CONCENTRATIONS OF POLYBROMINATED DIPHENYL ETHERS, HEXABROMOCYCLODODECANES AND TETRABROMOBISPHENOL-A IN BREAST MILK FROM UNITED KINGDOM WOMEN DO NOT DECREASE OVER TWELVE MONTHS
More informationUpdate zu EUCAST 2012 Cornelia Lass-Flörl
Update zu EUCAST 2012 Cornelia Lass-Flörl Frühjahrstagung 2012 Paul-Ehrlich-Gesellschaft Sektion Antimykotische Chemotherapie Bonn, 4./5. Mai 2012 Agenda 1. Breakpoints 2. Rationale documents and technical
More informationLC-MS/MS for the quantification of Peptide biomarker and mixture of closely related Protein in formulation
EUROPEAN BIOANALYSIS FORUM Barcelona, November 14-16, 2012 LC-MS/MS for the quantification of Peptide biomarker and mixture of closely related Protein in formulation Luc-Alain SAVOY CONTENT Part I: SGS
More informationA RAPID AND SENSITIVE ANALYSIS METHOD OF SUDAN RED I, II, III & IV IN TOMATO SAUCE USING ULTRA PERFORMANCE LC MS/MS
A RAPID AD SESITIVE AALYSIS METD OF SUDA RED I, II, III & IV I TOMATO SAUCE USIG ULTRA PERFORMACE LC MS/MS Choon Keow G, aomi TAAKA, Michelle KIM, Swee Lee YAP Waters Asia, Regional Technology Center,
More informationSimultaneous Analysis of Intact Human Insulin and Five Analogs in Human Plasma Using μelution SPE and a CORTECS UPLC Column
Simultaneous Analysis of Intact Human Insulin and Five Analogs in Human Plasma Using μelution SPE and a CORTECS UPLC Column Erin E. Chambers and Kenneth J. Fountain Waters Corporation, Milford, MA, USA
More informationComparison of a UPLC Method across Multiple UHPLC Systems
Comparison of a UPLC Method across Multiple UHPLC Systems Tanya Jenkins Waters Corporation, Milford, MA, U.S. INTRODUCTION In 2004, Waters introduced the ACQUITY UPLC System. Since this launch, many liquid
More informationPosterREPRINT SIMULTANEOUS QUANTIFICATION OF PSYCHOTHERAPEUTIC DRUGS IN HUMAN PLASMA BY TANDEM MASS SPECTROMETRY
OVERVIEW A simple and rapid LC-MS/MS method has been developed which allows the simultaneous quantification of a panel of commonly prescribed psychotherapeutic drugs in human plasma and whole blood. INTRODUCTION
More informationHigh resolution mass spectrometry for bioanalysis at Janssen. Current experiences and future perspectives
High resolution mass spectrometry for bioanalysis at Janssen. Current experiences and future perspectives Lieve Dillen Drug Safety Sciences Analytical Sciences, Non-regulated Bioanalysis Presentation outline
More informationOMCL Network of the Council of Europe QUALITY MANAGEMENT DOCUMENT
OMCL Network of the Council of Europe QUALITY MANAGEMENT DOCUMENT PA/PH/OMCL (10) 86 2R QUALIFICATION OF EQUIPMENT ANNEX 7: QUALIFICATION OF MASS SPECTROMETERS Full document title and reference Document
More informationNew Mass Spectrometry Tools to Transform Metabolomics and Lipidomics
New Mass Spectrometry Tools to Transform Metabolomics and Lipidomics July.3.13 Ken Miller Vice President of Marketing, Life Sciences Mass Spectrometry 1 The world leader in serving science Omics & the
More informationProbing for Packaging Migrants in a Pharmaceutical Impurities Assay Using UHPLC with UV and Mass Detection INTRODUCTION
Probing for Packaging Migrants in a Pharmaceutical Impurities Assay Using UHPLC with UV and Mass Detection Michael Jones Waters Corporation, Wilmslow, UK APPLICATION BENEFITS The ACQUITY Arc System is
More informationAgilent 7700x ICP-MS
Agilent 7700x ICP-MS Metals analysis Mid ppt to low ppb detection range Option to detect in four different gas modes to gain optimum detection of multiple metals or interferences in a sample Autosampler
More informationDetection, Confirmation, and Quantification of Chloramphenicol in Honey, Shrimp and Chicken Using the Agilent 6410 LC/MS Triple Quadrupole
Detection, Confirmation, and Quantification of Chloramphenicol in Honey, Shrimp and Chicken Using the Agilent LC/MS Triple Quadrupole Application Food Safety Authors Yanyan Fang Agilent Technologies (Shanghai),
More informationAgilent 6410 Triple Quadrupole LC/MS. Sensitivity, Reliability, Value
Agilent 64 Triple Quadrupole LC/MS Sensitivity, Reliability, Value Sensitivity, Reliability, Value Whether you quantitate drug metabolites, measure herbicide levels in food, or determine contaminant levels
More informationNew Solvent Grade Targeted for Trace Analysis by UHPLC-MS
New Solvent Grade Targeted for Trace Analysis by UHPLC-MS Subhra Bhattacharya, Deva H. Puranam, and Stephen C. Roemer Thermo Fisher Scientific Fisher Chemical, One Reagent Lane, Fair Lawn, NJ Material
More informationDon t miss a thing on your peptide mapping journey How to get full coverage peptide maps using high resolution accurate mass spectrometry
Don t miss a thing on your peptide mapping journey How to get full coverage peptide maps using high resolution accurate mass spectrometry Kai Scheffler, PhD BioPharma Support Expert,LSMS Europe The world
More informationJames Grech. Bachelor of Medical Science (UC) National Centre for Forensic Studies (NCFS) University of Canberra, ACT 2601
Evaluation of Enzyme-Linked ImmunoSorbent Assay and Liquid Chromatography-Tandem Mass Spectrometry as Screening and Confirmation Methods for the Detection of Synthetic Cannabinoids James Grech Bachelor
More informationFig. 1: Chemical structure of arachidonic acid COOH CH 3
Elimination of Matrix Effects Using Mixed-mode SPE Plate for High Throughput Analysis of Free Arachidonic Acid in Plasma by LC-MS/MS Wan Wang, Suzi Qin, Linsen Li, Warren Chen, Jerry Wang 179, Southern
More informationImproving Selectivity in Quantitative Analysis Using MS 3 on a Hybrid Quadrupole-Linear Ion Trap Mass Spectrometer
Improving Selectivity in Quantitative Analysis Using MS 3 on a Hybrid Quadrupole-Linear Ion Trap Mass Spectrometer Overview Increased selectivity is achieved in quantitative analysis by using MS 3. The
More informationThe use of mass spectrometry in lipidomics. Outlines
The use of mass spectrometry in lipidomics Jeevan Prasain jprasain@uab.edu 6-2612 utlines Brief introduction to lipidomics Analytical methodology: MS/MS structure elucidation of phospholipids Phospholipid
More informationNutrition: obtaining reliable biomarker data to study the health status of populations
Nutrition: obtaining reliable biomarker data to study the health status of populations Christine M. Pfeiffer, Ph.D. Chief, Nutritional Biomarkers Branch, DLS AAAS 2011 Annual Meeting Science Without Borders
More informationIdentification of Haemoglobinopathies by LC/MS
Identification of Haemoglobinopathies by LC/ Mark Harrison; Senior Scientist, ThermoFisher Scientific Sarah Battle; Senior Biomedical Scientist, Royal Hallamshire Hospital Introduction There are over 2
More informationApplication Note No. 119/2013 Determination of bisphenol A in preserved food SpeedExtractor E-916: Determination of bisphenol A in preserved food
Application Note No. 119/2013 Determination of bisphenol A in preserved food SpeedExtractor E-916: Determination of bisphenol A in preserved food using the SpeedExtractor E-916 1 Introduction Bisphenol
More informationMatrix-induced Signal Enhancement of Propamocarb in LC-MS/MS
Observations concerning a compound a matrix a method other Matrix-induced Signal Enhancement of Propamocarb in LC-MS/MS Reported by: EURL-SRM Version 1 (last update: 24.10.2012) Brief description of problem/observation/solution:
More informationValidation of a Reliable LC-MS/MS Method for Analysis of Simultaneously in Clinical Laboratory
Validation of a Reliable LC-MS/MS Method for Analysis of Simultaneously in Clinical Laboratory Five Steroids Atecla Nunciata Lopes Alves, Berenice Bilharinho Mendonca, Helena Panteliou Lima Valassi. Laboratório
More informationQuantification of lovastatin in human plasma by LC/ESI/MS/MS using the Agilent 6410 Triple Quadrupole LC/MS system
Quantification of lovastatin in human plasma by LC/ESI/MS/MS using the Agilent 641 Triple Quadrupole LC/MS system Application Note Clinical Research Author Siji Joseph Agilent Technologies Bangalore, India
More informationTentu Nageswara Rao et al. / Int. Res J Pharm. App Sci., 2012; 2(4): 35-40
International Research Journal of Pharmaceutical and Applied Sciences Available online at www.irjpas.com Int. Res J Pharm. App Sci., 2012; 2(4):35-40 Research Article Estimation of Fesoterodine fumarate
More informationRemoval of Triton X-100 from Plasma Samples Using Mixed-Mode Solid Phase Extraction (SPE)
Removal of Triton X- from Plasma Samples Using Mixed-Mode Solid Phase Extraction (SPE) Jonathan P. Danaceau, Erin Chambers, and Kenneth J. Fountain Waters Corporation, 34 Maple Street, Milford, MA USA
More informationUpdated Guidelines for Management of Candidiasis. Vidya Sankar, DMD, MHS April 6, 2017
Updated Guidelines for Management of Candidiasis Vidya Sankar, DMD, MHS April 6, 2017 Statement of Disclosure I have no actual or potential conflict of interest in relation to this presentation Outline
More informationSupporting information
Supporting information Figure legends Supplementary Table 1. Specific product ions obtained from fragmentation of lithium adducts in the positive ion mode comparing the different positional isomers of
More informationDesigner Fentanyls Drugs that kill and how to detect them. Cyclopropylfentanyl
Designer Fentanyls Drugs that kill and how to detect them Cyclopropylfentanyl Science for a safer world The in vitro metabolism of cyclopropylfentanyl Simon Hudson & Charlotte Cutler, Sport and Specialised
More informationAnalysis of anti-epileptic drugs in human serum using an Agilent Ultivo LC/TQ
Application Note Clinical Research Analysis of anti-epileptic drugs in human serum using an Agilent Ultivo LC/TQ Authors Jennifer Hitchcock 1, Lauren Frick 2, Peter Stone 1, and Vaughn Miller 2 1 Agilent
More informationSmall Molecule Science: Experimental designs for achieving ultra trace analysis
Small Molecule Science: Experimental designs for achieving ultra trace analysis Michael P. Balogh Principal scientist Waters Corporation 211 Waters Corporation 1 www.cosmoscience.org The Society for Small
More informationLC-MS/MS Method for the Determination of 21 Opiates and Opiate Derivatives in Urine
LC-MS/MS Method for the Determination of 21 Opiates and Opiate Derivatives in Urine J. Jones, S. Westwood, T. Liddicoat, L. Pereira, T. Edge Thermo Fisher Scientific, Manor Park, Runcorn, UK Overview Purpose:
More informationQuantitative Analysis of Drugs of Abuse in Urine using UHPLC Coupled to Accurate Mass AxION 2 TOF Mass Spectrometer
application Note Liquid Chromatography/ Mass Spectrometry Authors Sharanya Reddy Blas Cerda PerkinElmer, Inc. Shelton, CT USA Quantitative Analysis of Drugs of Abuse in Urine using UHPLC Coupled to Accurate
More information