Chemical Metrology for Human Health Assessment
|
|
- Morris West
- 5 years ago
- Views:
Transcription
1 Chemical Metrology for Human Health Assessment Metrology and Physical Constants International School of Physics Enrico Fermi Stephen A. Wise Analytical Chemistry Division Material Measurement Laboratory National Institute of Standards and Technology (NIST) Gaithersburg, Maryland USA
2 Development of Clinical SRMs 1960s 1970s 1980s 1990s 2000s Development of pure, crystalline standards for calibration Development of highly accurate and precise, isotope dilution GC/MS Definitive Methods for clinical analytes in serum Human serum-based SRMs certified for metabolites and electrolytes, e.g., SRM 909 Human Serum (lyophilized) New serum-based SRMs are frozen to reduce matrix effects. New efforts focus on reference methods for toxic metals and protein-based health markers Expanded efforts to develop reference methods and SRMs to address EU IVD Directive. New methods focus on isotope dilution with LC/MS and LC/MS/MS
3 Reference Methods & SRMs for Health Status Markers in Blood/Urine Reference Systems Currently in Place for Many Well-Defined Markers such as: Marker Calcium Chloride Cholesterol Creatinine Glucose Lithium Magnesium Potassium Sodium Triglycerides Urea Uric Acid Disease State Cancer, Blood Clotting Kidney Function Heart Disease Kidney Function Diabetes Antipsychotic Treatment Heart Disease Electrolyte Balance Electrolyte Balance Heart Disease Kidney Function Gout Characteristics of these markers: Relatively small well-defined molecular or elemental species Typically, can be determined using methodology wellstudied and characterized by NIST for many years Folic Acid Creatinine HO Estradiol OH C-Reactive Protein Reference Systems Being Developed for New Markers such as: Marker Troponin-I Cortisol C-Reactive Protein Estradiol Folates Glycated Hemoglobin Homocysteine TSH, T3,T4 Progesterone Speciated Iron PSA Disease State Myocardial Infarction Endocrine Function Risk of Heart Attack Hormone Balance Neural Tube Defects Diabetes Status Risk of Heart Disease Thyroid Function Hormone Balance Hemochromatosis Prostate Cancer Characteristics of some new markers: Proteins, peptides or DNA-based Heterogeneity and instability of analyte form Low concentration in blood or urine Cannot all be standardized using conventional analytical chemistry approaches HO I I O I T3 O NH 2 OH Glucose Progesterone
4 HIERARCHY OF CLINICAL METHODS Definitive Refe rence F ield Methods of Highest Accuracy and P recision; Tho roughly Tested for Bias; Generally not within Capabilities of Clinical Laboratories; Used to Assign Analyte Concentrations to Primary Refe rence Mate rials and to Validate Accuracy of Refe rence Methods. Carefully Tested Method of High Accuracy and P recision; Within Capabilities of Most Clinical Laboratories, but too Time Consuming for Routine Use; Used to Assign Analyte Concentrations of Secondary Reference Materials and Validate the Accuracy of Field Methods Methods Used for Routine Clinical Measure ments; Must be Sufficiently Accurate and P recise for Accurate Diagnosis; Must be Simple, Rugged, and Cost Effective
5 Definitive Methods and Traceability Definitive Method is defined as: A method of exceptional scientific status, which is sufficiently accurate to stand alone in the determination of a given property for the Certification of a Reference Material. Such a method must have a firm theoretical foundation so that systematic error is negligible relative to the intended use. Analyte masses (amounts) or concentrations must be measured directly in terms of the base units of measurements, or indirectly related through sound theoretical equations. Definitive methods, together with Certified Reference Materials, are primary means for transferring accuracy -- i.e., establishing traceability. Traceability is defined as: The property of a result or measurement whereby it can be related to appropriate standards, generally international or national standards, through an unbroken chain of comparisons.
6 Definitive Methods for Clinical Analytes NIST developed a series of definitive methods for clinical analytes (e.g., cholesterol, glucose, uric acid, etc.) during the 1980s and 1990s Methods are based upon isotopedilution gas chromatography/mass spectrometry (GC/MS) Methods utilize a stable isotopelabeled internal standard Analytes are converted to a stable derivative for GC/MS
7 Isotope Dilution/Mass Spectrometry-based Definitive Methods Addition of Known Mass of Isotope labeled Material to Known Mass of Serum (or other matrix) Isolation of the Analyte from the Matrix Further Separation From Potential Interferences Tests and Corrections for Blanks and Interferences Precise Isotope Ratio Measurements of the Labeled and Unlabeled Forms Calibration of the Mass Spectrometer With Known Mixtures of Primary Reference Material and Labeled Material Calculate Results and Provide Complete Uncertainty Statement
8 CHOLESTEROL DEFINITIVE METHOD SAMPLE PREPARATION Weigh serum sample containing 0.5 mg cholesterol, add known mass of cholesterol- 13 C 3 in ethanol, and equilibrate All alcoholic KOH and heat at 37 deg for 3 h to saponify esters Extract with 10 ml hexane, evaporate under N 2, and dissolve in 1 ml methanol Take 0.1 ml, evaporate methanol, redissolve in BSA, and heat at 60 deg for 0.5h CALIBRATION STANDARDS Prepare primary standard solution by dissolving known mass of SRM 911b Cholesterol (purity %) in known mass of ethanol Add constant mass of cholesterol- 13 C 3 in ethanol to series of tubes and add masses of primary standard solution to the tubes such that the unlabeled/labeled cholesterol ratio ranges from 0.8 to 1.2.
9 Number of patients Bias in Cholesterol Measurement Effects Medical Decision-Making Cholesterol, mg/dl Cholesterol Frequency Distribution of >20,000 persons (with +1%, +3% and +10% limits around 240 mg/dl criteria point) If measurement Positives (>240 mg/dl) Predicted Change bias were: per 1000 in Positives/ % bias % bias % bias % bias % bias % bias % bias
10 ID GC/MS Definitive Methods for Clinical Analytes Cholesterol A. Cohen et al., Clin. Chem., 26, (1980) R. Schaffer et al., Clin. Chem., (1982) Glucose E. White et al., Biomed. Mass Spectrom., 9, (1982) Urea M.J. Welch et al., Anal. Chem., 56, (1984) Creatinine M.J. Welch et al., Anal. Chem., 58, (1986) Uric Acid P. Ellerbe et al., Anal. Chem., 62, (1990) Total Glycerides and Triglycerides Ellerbe et al, Clin. Chem. 41/3, (1995)
11 New Methods for Clinical Analytes Recent trend toward development of liquid chromatography/mass spectrometry (LC/MS and LC/MS/MS) methods for clinical analytes Sample preparation often simplified Better suited for thermally labile analytes Derivatization usually not required Mass spectrometry methods increasingly adopted by clinical laboratories Reference Measurement Procedures (RMPs)
12 Creatinine Marker for Kidney Disease SRM 967 Creatinine in Human Serum Kidney Failure in the U.S. Creatinine in serum is a diagnostic marker for chronic kidney disease (CKD) Physicians use serum creatinine levels to calculate egfr GFR (glomerular filtration rate) is indicative of ability of kidneys to filter wastes from blood Errors in creatinine measurement will affect egfr and accuracy of positive or negative diagnosis of CKD
13 GC/MS Definitive Method for Creatinine Definitive method based on isotope-dilution GC/MS Add IS*, equilibrate overnight Ion-exchange resin to remove creatine Elute creatinine, remove water Derivatize GC/MS analysis *Internal standard is creatinine- 13 C 2
14 LC/MS Reference Measurement Procedure (RMP) for Creatinine New LC/MS method developed based on work of Stokes and O Connor (LGC) Add IS*, equilibrate overnight Protein precipitation, remove supernatant Solvent exchange, filter, LC/MS analysis C18 Chromatographic column Mobile phase is 10 mm ammonium acetate/acetonitrile Positive mode electrospray ionization Selective ion monitoring of (M+H) + ions at m/z 114 and 117 *Internal standard is creatinine-d 3
15 -4 MSD TIC (x 10 ) -4 MSD TIC (x 10 ) -4 MSD TIC (x 10 ) LC/MS RMP for Creatinine 3 2 Creatinine m/z Time (min) 3 2 Creatinine-d m/z Time (min) Time (min) Creatine m/z 132
16 ID GC/MS and ID LC/MS Method Comparison GC-MS Method LC-MS Method Pool 1 Pool 2 Pool 1 Pool 2 ( m mol/l) ( m mol/l) ( m mol/l) ( m mol/l) Mean Mean SD SD CV(%) CV(%) N.G. Dodder, S.S-C. Tai, L.T. Sniegoski, N.F. Zhang, M.J. Welch, Clin. Chem. 53: (2007)
17 Recent SRMs for Health Status Markers SRMs Recently Issued SRM 1951b Cholesterol in Human Serum SRM 965b Glucose in Human Serum SRM 956b Electrolytes in Human Serum SRM 2721 Cardiac Troponin I SRM 1955 Homocysteine and Folate in Human Serum SRM 967a Creatinine in Frozen Human Serum SRM 927d Bovine Serum Albumin SRM 971 Hormones in Human Serum SRM 972 Vitamin D Metabolites in Serum SRM 3950 Vitamin B 6 in Human Serum SRMs In Progress SRM 3951 Vitamin B 12 in Human Serum
18 Why are Nutritional Biomarkers Important? Identifying individuals with vitamin deficiencies Not everyone responds the same way to nutrient exposure Difficult to quantify intake based on diet and self-reporting Understanding biochemical pathways Population surveys and public health policies Data is meaningful only if the measurement methods used are accurate
19 Why is Vitamin D Important? Task force recommends against Vitamin D, calcium supplements Shedding light on vitamin D deficiency crisis Low levels are blamed for many of our ills. But how much is really enough? Vitamin D is essential for maintaining calcium homeostasis Both Calcium and vitamin D are needed for bone health Vitamin D deficiency associated with rickets and osteomalacia Potential link between vitamin D deficiency and increased disease risk
20 Vitamin D Vitamin D occurs primarily in two forms vitamin D 2 and vitamin D 3 Sunlight Food Dietary Supplements Production of vitamin D 3 in skin Contains vitamin D 2 or D 3 Contains vitamin D 2 or D 3 Hydroxylation in liver to 25(OH)D Hydroxylation in kidney to 1,25(OH) 2 D
21 Measurement Techniques for Vitamin D Immunoassay Antibody specificity is high, cross-reactivity may occur No independent confirmation of analyte identity Gas Chromatography (GC-MS) Liquid Chromatography LC-UV Mass Spectrometry (LC-MS) Tandem Mass Spectrometry (LC-MS/MS)
22 Mass Spectrometry-Based Methods for Determination of Vitamin D Metabolites The 3-epimer of 25(OH)D 3 co-elutes with 25(OH)D 3 on C18 columns 25(OH)D 3 and 3-epi-25(OH)D 3 have the same MS/MS fragmentation patterns Initially the 3-epimer was thought to be only found in infants (Singh et al.) 25(OH)D 2 25(OH)D 3 3-epi-25(OH)D 3
23 LC-MS/MS Methodology for 25(OH)D Add water and ISTDs* Equilibrate 1 hr, adjust ph to 9.8 Extract with hexane:ethyl acetate Dry with N 2, dilute with methanol LC-MS/MS analysis * The internal standards were 2 H 3-25(OH)D 2 and 2 H 3-25(OH)D 3
24 NIST LC-MS/MS Methodology 25(OH)D 3 SRM 972 Level 1 ~ 60 nmol/l APCI MS using cyano column with methanol:water mobile phase 3-epi-25(OH)D 3 fully resolved from 25(OH)D 3 (separation based on work of Lensmeyer et al.) Labeled 3-epi-25(OH)D 3 now available for use as internal standard Susan Tai et al., Analytical Chemistry, 2010 Method approved by JCTLM as Reference Measurement Procedure
25 NIST LC-MS/MS Methodology 25(OH)D 2 SRM 972 Level 3 SRM 972 Level 4 ~ 65 nmol/l ~ 6 nmol/l
26 The Epi Question? (OH)D 3 3-epi-25(OH)D 3 The 3-epimer of 25(OH)D 3 appears to be present in nearly all adult sera but its concentration varies
27 Design of SRM 972 Vitamin D in Human Serum Level 1 65 ± 15 nmol/l 25-hydroxyvitamin D 3 ( normal ) Level 2 Blend of normal serum and horse serum to obtain approximately half the level of 25-hydroxyvitamin D 3 in the normal pool (35 ± 5 nmol/l) Level 3 Normal serum spiked with an equivalent amount of 25- hydroxyvitamin D 2 Level 4 Normal serum spiked with 3-epi-25-hydroxyvitamin D 3 Goal was to have serum pools that presented different analytical challenges
28 Assigned Values for SRM (OH)D 2 25(OH)D 3 3-epi- 25(OH)D 3 Level ± 0.20 Level ± 0.08 Level ± 1.9 Level ± ± ± ± ± ± ± ± ± 1.1 Certified and reference values obtained from combination of results from multiple methods: LC-MS (NIST), LC- MS/MS (NIST) and LC-MS/MS (CDC). Certified values are shown in bold. All data in ng/g.
29 Vitamin D Metabolites QA Program o o o o Two exercises per year, no cost for participation Not a proficiency program NIST value assigned by ID MS Results do not support common belief that LC- MS/MS always provides higher results Results for total 25(OH)D in a non-fortified sample Data courtesy of M. Bedner and K. Lippa
30 Vitamin D Metabolites QA Program o o o Fortification has been used to prepare multi-level reference materials for other clinical analytes (creatinine, etc.) Spiking serum with 25(OH)D may not be an appropriate way to prepare control materials Analyte may bind to other proteins (HSA) instead of DBP This sample had been fortified with 25(OH)D 2. Results are grouped into two distinct populations, suggesting not all techniques see the sample the same way. Data courtesy of M. Bedner and K. Lippa
31 Human Nutritional Assessment SRMs In Progress SRM 3949 Folate Vitamers in Frozen Human Serum SRM 3950 Vitamin B 6 metabolites in Frozen Human Serum SRM 3951 Vitamin B 12 in Frozen Human Serum SRM 2378 Fatty Acids in Frozen Human Serum
32 Is ID GC/MS Required? Comparison of ID GC/MS vs. GC-FID and Titrimetry for determination of ethanol in water NIST GC-FID (IS = n-proh) NMIA ID GC/MS ( 13 C EtOH) NML-CSIR Titrimetry Certified Value Mean stdev rsd % % % ± % Mean stdev rsd % % % ± % Mean stdev rsd % % % ± %
33 ID GC/MS vs. ID LC/MS (or MS/MS) Requirements for quantification using internal standards for GC/MS vs. LC/MS are different For GC/MS internal standard does not need to elute with the analyte for good precision For LC/MS (or MS/MS) internal standard should elute with or near analyte to achieve best precision Precision for both can be similar under optimal conditions
34 Isotope Dilution MS - Conclusions Isotope dilution MS-based GC or LC analyses are the recommended approach for organic analysis in complex matrices if labeled standards are available In simpler matrices ID MS methods may not be required Use of ID MS methods does not guarantee that the results are accurate
35
CCQM-K6: Key Comparison on the Determination of Cholesterol In Serum* Final Report December 2001
CCQM-K6: Key Comparison on the Determination of Cholesterol In Serum* INTRODUCTION Final Report December 2001 Michael J. Welch, Reenie M. Parris, Lorna T. Sniegoski, and Willie E. May Analytical Chemistry
More informationReference Material Institute for Clinical Chemistry Standards (ReCCS)
Certified Reference Material for Measurement of Glucose, Creatinine, Uric Acid and Urea-N in Human Serum JCCRM Certificate of Analysis Intended use This Certified Reference Material CRM is intended primarily
More informationCCQM-K63.a,b. Non-Peptide Hormones in Serum: Cortisol and Progesterone. Final Report: 20-Jan-2010
CCQM-K63.a,b Non-Peptide Hormones in Serum: Cortisol and Progesterone Final Report: 20-Jan-2010 Susan S.-C. Tai and David L. Duewer National Institute of Standards and Technology (NIST) Gaithersburg, MD
More informationCCQM-K11: Key Comparison on the Determination of Total Glucose in Human Serum. Final Report May 2003
CCQM-K11: Key Comparison on the Determination of Total Glucose in Human Serum Final Report May 2003 Michael Welch, Lorna Sniegoski, Reenie Parris, and Willie May Analytical Chemistry Division Chemical
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 informationCCQM-K12: Key Comparison on the Determination of Creatinine in Human Serum. Final Report March 2003
CCQM-K12: Key Comparison on the Determination of Creatinine in Human Serum Final Report March 2003 Michael Welch, Curtis Phinney, Reenie Parris, and Willie May Analytical Chemistry Division Chemical Science
More informationSCIEX Vitamin D 200M Assay for the Topaz System
The First FDA-Cleared LC-MS/MS Assay for Vitamin D SCIEX Vitamin D 200M Assay for the Topaz System The first FDA-cleared LC-MS/MS assay for Vitamin D Vitamin D is an important building block for human
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 informationQuestionnaire. Traceability in EQA. Traceability
Questionnaire in EQA QUESTIONNAIRE ON TRACEABILITY QUESTIONNAIRE ON TRACEABILITY GENERAL INFORMATION Name EQA organisation Country Specify the total number of measurands in the schemes of your EQA organisation
More informationAll stocks and calibration levels were prepared in water: methanol (50:50) v/v to cover range of all steroid concentrations (refer Table 1).
Application LCMS-8040 Simultaneous determination of 11 steroids and Vitamin D2/D3 in human serum using LC/MS/MS - Introduction Quantification of endogenous hormonal steroids and their precursors is essential
More informationReference Material Institute for Clinical Chemistry Standards (ReCCS)
Reference Material Institute for Clinical Chemistry Standards (ReCCS) Certified Reference Material for Measurement of Total Cholesterol and Glycerides in Human Serum Certificate of Analysis Intended use
More informationIntroduction Bull. Korean Chem. Soc. 2013, Vol. 34, No. 6 Hwa Shim Lee et al.
1698 Bull. Korean Chem. Soc. 013, Vol. 34, No. 6 Hwa Shim Lee et al. http://dx.doi.org/10.501/bkcs.013.34.6.1698 Development and Validation of Primary Method for the Determination of Glucose in Human Serum
More informationExternal Quality Assessment for Calibration Laboratories in Laboratory Medicine - RELA -
External Quality Assessment for Calibration Laboratories in Laboratory Medicine - RELA - Anja Kessler Bonn, Germany 1 RELA Surveys www.dgkl-rfb.de 2 RELA Annual Process Each participant receives two different
More informationStandardization of. S.M.Boutorabi DCLS,PhD
Standardization of Creatinine Assay S.M.Boutorabi DCLS,PhD Chronic kidney disease (CKD) is a major public health problem in developed countries Why measure serum creatinine? Jaffe Reaction Creatinine +picric
More informationLaboratory Medicine Standardization Activity in Japan
JCTLM 15/11/2005 Sevres, Paris oratory Medicine Standardization Activity in Japan National Institute Metrology of Japan (NMIJ) Koichi Chiba Fujirebio Inc. Katsuhiko Yamamoto University of Tsukuba Katsuhiko
More informationAnalytical Method for 2, 4, 5-T (Targeted to Agricultural, Animal and Fishery Products)
Analytical Method for 2, 4, 5-T (Targeted to Agricultural, Animal and Fishery Products) The target compound to be determined is 2, 4, 5-T. 1. Instrument Liquid Chromatograph-tandem mass spectrometer (LC-MS/MS)
More informationDetermination of 6-Chloropicolinic Acid (6-CPA) in Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection. EPL-BAS Method No.
Page 1 of 10 Determination of 6-Chloropicolinic Acid (6-CPA) in Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection EPL-BAS Method No. 205G881B Method Summary: Residues of 6-CPA are
More informationCortisol Assays. The Good, The Bad and The Indifferent. David Ducroq. Cardiff and Vale ulhb WEQAS. Unit 6, Parc Tŷ Glas. Llanishen.
Cortisol Assays The Good, The Bad and The Indifferent David Ducroq Cardiff and Vale ulhb WEQAS Unit 6, Parc Tŷ Glas Llanishen Cardiff www.weqas.com Summary Brief overview of current methods and challenges
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 informationElectrolyte Analyzer with Ion-Selective Electrode and Blood Gas analyzer
Biochemistry & Fundamental Reference Laboratory, Yokohama Our Head Office and Biochemistry Reference Laboratory moved to Yokohama with aims to have further development on the 21 st September, 2018. [Reference
More informationHarmonization of Clinical Laboratory Results is Essential for Quality Patient Care
Harmonization of Clinical Laboratory Results is Essential for Quality Patient Care Greg Miller, PhD Virginia Commonwealth University Richmond, VA Presented at the National Association of Chronic Disease
More informationBiochemistry Adult Reference Ranges
Certified correct on 28/06/2016 Biochemistry Adult Reference Ranges Test Reference range Units Reference range from Traceable to standard reference material Albumin 35 50 g/l Pathology IRMM ERM-DA470k/IFCC
More informationCertificate of Analysis JCCRM 811-1
Reference Material Institute for Clinical Chemistry Standards (ReCCS) Certificate of Analysis Certified Reference Material for Measurement of Uric Acid in Human Serum JCCRM 811-1 Intended use This certified
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 informationAuthors. Abstract. Introduction. Environmental
Determination of Ultratrace Amitrol in Water Samples by in situ Derivatization-Solid Phase Extraction-Liquid Chromatography-Mass Selective Detector Application Environmental Authors Gerd Vanhoenacker,
More informationRapid and Robust Detection of THC and Its Metabolites in Blood
Rapid and Robust Detection of THC and Its Metabolites in Blood Application Note Forensics/Doping Control Author Stephan Baumann Agilent Technologies, Inc. Santa Clara CA 95051 USA Abstract A robust method
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 informationAnalysis of Testosterone, Androstenedione, and Dehydroepiandrosterone Sulfate in Serum for Clinical Research
Analysis of Testosterone, Androstenedione, and Dehydroepiandrosterone Sulfate in Serum for Clinical Research Dominic Foley, Michelle Wills, and Lisa Calton Waters Corporation, Wilmslow, UK APPLICATION
More informationTowards Improved Reliability in Laboratory Medicine. Universal Metrological Traceability
Towards Improved Reliability in Laboratory Medicine Universal Metrological Traceability Lothar Siekmann Medical Faculty University of Bonn Institute of Clinical Chemistry and Pharmacology Reference-Institute
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 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 informationIntegration of steroids analysis in serum using LC-MS/MS with full-automated sample preparation
PO-CON69E Integration of steroids analysis in serum using LC-MS/MS with full-automated sample preparation MSACL 6 EU Stéphane Moreau, Daisuke Kawakami, Toshikazu Minohata Shimadzu Europe GmbH, Duisburg,
More informationChallenges of implementing JCTLM methods in the routine Clinical Laboratories. R.J. Singh, Ph.D. Mayo Clinic
Challenges of implementing JCTLM methods in the routine Clinical Laboratories R.J. Singh, Ph.D. Mayo Clinic 100s of Millions of 25-OH Vitamin D test have been run. Total 25-OH Vitamin D test is not a useful
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 informationApplication Note. Author. Abstract. Introduction. Food Safety
Determination of β2-agonists in Pork with SPE eanup and LC-MS/MS Detection Using Agilent BondElut PCX Solid-Phase Extraction Cartridges, Agilent Poroshell 120 column and Liquid Chromatography-Tandem Mass
More informationMeasuring Phytosterols in Health Supplements by LC/MS. Marcus Miller and William Schnute Thermo Fisher Scientific, San Jose, CA, USA
Measuring Phytosterols in Health Supplements by LC/MS Marcus Miller and William Schnute Thermo Fisher Scientific, San Jose, CA, USA Overview Purpose: Develop a method for the extraction of phytosterols
More informationAnalysis of Acrylamide in French Fries using Agilent Bond Elut QuEChERS AOAC kit and LC/MS/MS
Analysis of Acrylamide in French Fries using Agilent Bond Elut QuEChERS AOAC kit and LC/MS/MS Food Application Author Fadwa Al-Taher Institute for Food Safety and Health Illinois Institute of Technology
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 informationDetermination of β2-agonists in Pork Using Agilent SampliQ SCX Solid-Phase Extraction Cartridges and Liquid Chromatography-Tandem Mass Spectrometry
Determination of β2-agonists in Pork Using Agilent SampliQ SCX Solid-Phase Extraction Cartridges and Liquid Chromatography-Tandem Mass Spectrometry Application Note Food Safety Authors Chenhao Zhai Agilent
More informationCertified Reference Materials - A Path to Traceable Chemical Measurements
Certified Reference Materials - A Path to Traceable Chemical Measurements Paul Armishaw 5 May 2016 What I plan to talk about Why traceability so measurements can be compared Traceable to what? SI units
More informationVitamin D Metabolite Analysis in Biological Samples Using Agilent Captiva EMR Lipid
Vitamin D Metabolite Analysis in Biological Samples Using Agilent Captiva EMR Lipid Application Note Clinical Research Authors Derick Lucas and Limian Zhao Agilent Technologies, Inc. Abstract Lipids from
More informationRapid Analysis of Water-Soluble Vitamins in Infant Formula by Standard-Addition
Rapid Analysis of Water-Soluble Vitamins in Infant Formula by Standard-Addition Evelyn Goh Waters Pacific, Singapore APPLICATION BENEFITS This method allows for the simultaneous analysis of 12 water-soluble
More informationFast quantitative Forensic Analysis of THC and its Metabolites in Biological Samples using Captiva EMR- Lipid and LC/MSMS
Fast quantitative Forensic Analysis of THC and its Metabolites in Biological Samples using Captiva EMR- Lipid and LC/MSMS Christophe Deckers, M.Sc. Sample prep Application Scientist Types of ``Interferences``
More informationLutein Esters from Tagetes Erecta
Residue Monograph prepared by the meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), 82 nd meeting 2016 Lutein Esters from Tagetes Erecta This monograph was also published in: Compendium
More informationExtraction of a Comprehensive Steroid Panel from Human Serum Using ISOLUTE. SLE+ Prior to LC/MS-MS Analysis
Application Note AN890 Extraction of a Comprehensive Steroid Panel from Human Serum Using ISOLUTE SLE+ Page Extraction of a Comprehensive Steroid Panel from Human Serum Using ISOLUTE SLE+ Prior to LC/MS-MS
More informationLC-MS/MS Method for the Determination of Tenofovir from Plasma
LC-MS/MS Method for the Determination of Tenofovir from Plasma Kimberly Phipps, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 687 Key Words SPE, SOLA CX, Hypersil GOLD, tenofovir Abstract
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 informationProficiency testing performance of Turkish laboratories on determination of relative composition of fatty acids in sunflower oil
ORIGINAL ARTICLE J. Chem. Metrol. 11:2 (2017) 40-45 Proficiency testing performance of Turkish laboratories on determination of relative composition of fatty acids in sunflower oil Hasibe Yilmaz 1*, Simay
More informationIsotope Dilution Mass Spectrometry as a Candidate Definitive Method for Determining Total Glycerides and Triglycerides in Serum
CLIN. CHEM. 41/3, 397-404 (1995) #{149} Lipids and Lipoproteins Isotope Dilution Mass Spectrometry as a Candidate Definitive Method for Determining Total Glycerides and Triglycerides in Serum Pofly Ellerbe,
More informationA Robustness Study for the Agilent 6470 LC-MS/MS Mass Spectrometer
A Robustness Study for the Agilent 7 LC-MS/MS Mass Spectrometer Application Note Clinical Research Authors Linda Côté, Siji Joseph, Sreelakshmy Menon, and Kevin McCann Agilent Technologies, Inc. Abstract
More informationFast determination of residual glycerol and glycerides in biodiesel by SFC/MS using the Agilent 1260 Infinity Analytical SFC System
Fast deteration of residual glycerol and glycerides in biodiesel by SFC/MS using the Agilent 126 Infinity Analytical SFC System Application Note Petrochemical Authors Maria Rambla Alegre, Melissa N. Dunkle,
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 informationThe setup and validation of an LC-MS/MS assay of Androstenedione & Testosterone a labs experience
The setup and validation of an LC-MS/MS assay of Androstenedione & Testosterone a labs experience Keith Mulready Specialist Senior Medical Scientist Why measure Testosterone? Hypogonadism in Males Cancer
More informationLaboratory and Measurement Issues. Greg Miller, PhD Virginia Commonwealth University Richmond, VA
Laboratory and Measurement Issues Greg Miller, PhD Virginia Commonwealth University Richmond, VA Outline Serum/plasma creatinine Serum/plasma cystatin C Urine albumin Urine protein Creatinine standardization
More informationComplete Medical History
Lab Results for Ben Greenfield Last Test Date: Your medical history is not complete. Complete Medical History Complete Medical History What's Next Blood Draw Blood draw scheduled Complete your medical
More informationFat Content Determination Methods Teresa McConville Chem 311 Dr. Weisshaar
Fat Content Determination Methods Teresa McConville Chem 311 Dr. Weisshaar The methods used in determination of fat content in foods are as varied as the sample matrices. This is an overview of a few methods
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 informationDetermination of Benzodiazepines in Urine by CE-MS/MS
Determination of Benzodiazepines in Urine by CE-MS/MS Application ote Forensic Toxicology Authors audimir Lucio do Lago Department of Fundamental Chemistry, Institute of Chemistry University of São Paulo,
More information25-Hydroxyvitamin D assay performance. Graham Carter Imperial College
25-Hydroxyvitamin D assay performance Graham Carter Imperial College www.deqas.org Outline of Talk 1. DEQAS: Organization and Objectives 2. Mean Assay Bias and Precision 3. Bias of individual samples
More informationDetermination of Amphetamine and Derivatives in Urine
Determination of Amphetamine and Derivatives in Urine Using a Modified QuEChERS and Capillary Electrophoresis Tandem Mass Spectrometry Analysis Application Note Authors Vagner B. dos Santos and Claudimir
More informationWorkflow for Screening and Quantification of the SAMHSA (NIDA) Panel in Urine Using UHPLC-TOF
APPLICATIO OTE Liquid Chromatography/ Mass Spectrometry Authors: Avinash Dalmia Joanne Mather PerkinElmer, Inc. Shelton, CT Workflow for Screening and Quantification of the SAMHSA (IDA) Panel in Urine
More informationSUPPLEMENTARY APPENDIX. COU-AA-301 enrolled men with pathologically confirmed mcrpc who had received previous
SUPPLEMENTARY APPENDIX Methods Subjects COUAA30 enrolled men with pathologically confirmed mcrpc who had received previous treatment with docetaxel chemotherapy and had documented PSA progression according
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 informationThe Development of LC/MS Methods for Determination of MDMA (Ecstasy) and Metabolites in Biological Samples
WA20714 The Development of LC/MS Methods for Determination of MDMA (Ecstasy) and Metabolites in Biological Samples Michael S. Young and Kevin M. Jenkins Waters Corporation, 34 Maple Street, Milford, MA
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 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 informationGeneral Chemistry Scheme Guide
General Chemistry Scheme Guide Copyright WEQAS. All rights reserved. No part of this document may be reproduced or utilised in any form without permission from WEQAS Contents. Scheme details and repertoire.....
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 informationFinal Report. CCQM K62: Nutrients in Infant/Adult Formula Vitamins
Final Report CCQM K62: Nutrients in Infant/Adult Formula Vitamins Katherine E. Sharpless, Catherine A. Rimmer, Karen W. Phinney, Bryant C. Nelson, David L. Duewer, and Stephen A. Wise National Institute
More informationCertified reference materials for ensuring traceability: From experience with steroids and peptide
1 Certified reference materials for ensuring traceability: From experience with steroids and peptide Akiko Takatsu National Metrology Institute of Japan (NMIJ), National Institute of Advanced Industrial
More informationApplication Note. Abstract. Authors. Pharmaceutical
Analysis of xycodone and Its Metabolites-oroxycodone, xymorphone, and oroxymorphone in Plasma by LC/MS with an Agilent ZRBAX StableBond SB-C18 LC Column Application ote Pharmaceutical Authors Linda L.
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 informationStandardization and Certification of the ADVIA Centaur Vitamin D Total Assay
Standardization and Certification of the ADVIA Centaur Vitamin D Total Assay Authors: James Freeman Paul Sibley, PhD Neil Parker, MSc Ryan Spears Kimberly S. Wilson H. Roma Levy, MS Affiliations: Siemens
More informationDEXAMETHASONE. First draft prepared by Bruno LE BIZEC, Nantes, France
DEXAMETHASONE First draft prepared by Bruno LE BIZEC, Nantes, France ADDENDUM to the Dexamethasone monograph prepared by the 42 nd, 43 rd and 50 th meetings of the Committee and published in FAO Food and
More informationAdams Memorial Hospital Decatur, Indiana EXPLANATION OF LABORATORY TESTS
Adams Memorial Hospital Decatur, Indiana EXPLANATION OF LABORATORY TESTS Your health is important to us! The test descriptions listed below are for educational purposes only. Laboratory test interpretation
More informationSupplementary Information. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse by a
Supplementary Information Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse by a High-throughput Targeted Metabolomics Approach Nanyang Yu, Si Wei, *, Meiying Li, Jingping
More informationThe Development of LC/MS Methods for Determination of Polar Drugs of Abuse in Biological Samples
WA20259 The Development of LC/MS Methods for Determination of Polar Drugs of Abuse in Biological Samples Michael S. Young and Kevin M. Jenkins Waters Corporation, 34 Maple Street, Milford, MA 01757 Introduction
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 informationRapid Analysis of Bisphenols A, B, and E in Baby Food and Infant Formula Using ACQUITY UPLC with the Xevo TQD
Rapid Analysis of Bisphenols A, B, and E in Baby Food and Infant Formula Using ACQUITY UPLC with the Xevo TQD Claude R. Mallet Waters Corporation, Milford, MA, USA A P P L I C AT ION B E N E F I T S This
More informationDevelopment and Validation of a Liquid Chromatography- Mass Spectrometry method for analysis of Oxysterols in Human Plasma
1 Development and Validation of a Liquid Chromatography- Mass Spectrometry method for analysis of Oxysterols in Human Plasma Rohini Narayanaswamy University At Buffalo, The State University of New York
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 informationMethod Validation for the Analysis of Multiple Weight Loss Drugs in Dietary Supplement Materials by LC-MS/MS
Journalof RegulatoryScience htp:\journalofregulatoryscience.org Journal of Regulatory Science 02 (2015) 15 19 Regulatory Science Method Validation for the Analysis of Multiple Weight Loss Drugs in Dietary
More informationBias in clinical chemistry. Elvar Theodorsson EFLM and Linköping University
Bias in clinical chemistry Elvar Theodorsson EFLM and Linköping University Bias a controversial subject Different perspectives Reseachers Users Regulatory bodies Standardisation organisations Metrologists
More informationDiscrepancy between Vitamin D Total Immunoassays due to Various Cross-reactivities
J Bone Metab ;22:7-112 http://dx.doi.org/.105/jbm..22.3.7 pissn 2287-6375 eissn 2287-7029 Original Article Discrepancy between Vitamin D Total Immunoassays due to Various Cross-reactivities Jun Hyung Lee,
More informationMultiphasic Blood Analysis
Understanding Your Multiphasic Blood Analysis Test Results Mon General thanks you for participating in the multiphasic blood analysis. This test can be an early warning of health problems, including coronary
More informationEnhanced LC-MS Sensitivity of Vitamin D Assay by Selection of Appropriate Mobile Phase
Enhanced LC-MS Sensitivity of Vitamin D Assay by Selection of Appropriate Mobile Phase Subhra Bhattacharya and Stephen C. Roemer Thermo Fisher Scientific Global Chemicals, Fair Lawn, NJ, USA AbstrAct Liquid
More information4.5 Minute Analysis of Benzodiazepines in Urine and Whole Blood Using LC/MS/MS and an Ultra Biphenyl Column
Clinical, Forensic & Toxicology Applications 4.5 Minute Analysis of Benzodiazepines in Urine and Whole Blood Using LC/MS/MS and an Ultra Biphenyl Column By Amanda Rigdon Abstract A rapid, sensitive method
More informationDetection of Low Level of Chloramphenicol in Milk and Honey with MIP SPE and LC-MS-MS
Detection of Low Level of Chloramphenicol in Milk and Honey with MIP SPE and LC-MS-MS Olga Shimelis, An Trinh, and Michael Ye Supelco, Div. of Sigma-Aldrich, Bellefonte, PA T407125 Introduction Molecularly
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 informationHigh Throughput Extraction of Opiates from Urine and Analysis by GC/MS or LC/MS/MS)
High Throughput Extraction of Opiates from Urine and Analysis by GC/MS or LC/MS/MS) Michael Rummel, Matthew Trass, Michael Campognone, and Sky Countryman Phenomenex, Inc., 411 Madrid Avenue, Torrance,
More informationLC/MS Biomarker Assay Validation Strategies Using Surrogate Matrix and Surrogate Analyte Approaches
LC/MS Biomarker Assay Validation Strategies Using Surrogate Matrix and Surrogate Analyte Approaches Barry R. Jones 1, Gary A. Schultz 1, Steve Lowes 1, James A. Eckstein 2, Barry S. Lutzke 2, Bradley L.
More informationMethodology Report Total 25-Hydroxyvitamin D Determination by an Entry Level Triple Quadrupole Instrument: Comparison between Two Commercial Kits
BioMed Volume 213, Article ID 27426, 5 pages http://dx.doi.org/1.1155/213/27426 Methodology Report Total 25-Hydroxyvitamin D Determination by an Entry Level Triple Quadrupole Instrument: Comparison between
More informationDetermination of red blood cell fatty acid profiles in clinical research
Application Note Clinical Research Determination of red blood cell fatty acid profiles in clinical research Chemical ionization gas chromatography tandem mass spectrometry Authors Yvonne Schober 1, Hans
More informationAnalyte Specimen Demographic Reference Range Units
Acetone Negative titer Alanine aminotransferase (ALT/SGPT) 10-49 U/L Albumin 3.2-4.8 g/dl Alcohol < 10 Alpha-fetoprotein (AFP) < 1.3-8.1 ng/ml Alkaline phosphatase 0 7 days 7 30 days 1 3 3 6 6 12 1 3 3
More informationExtraction of 25-hydroxy Vitamin D from Serum Using ISOLUTE. PLD+ Prior to LC-MS/MS Analysis
Application Note AN842.V. Extraction of 25-hydroxy Vitamin D from Serum Using ISOLUTE PLD+ Prior to LC-MS/MS Analysis Page Extraction of 25-hydroxy Vitamin D from Serum Using ISOLUTE PLD+ Prior to LC-MS/MS
More informationDIRECT EXTRACTION OF BENZODIAZEPINE METABOLITE WITH SUPERCRITICAL FLUID FROM WHOLE BLOOD
DIRECT EXTRACTION OF BENZODIAZEPINE METABOLITE WITH SUPERCRITICAL FLUID FROM WHOLE BLOOD Kenichi TAKAICHI, Shuji SAITOH, Yoshio KUMOOKA, Noriko TSUNODA National Research Institute of Police Science, Chiba,
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 informationComparison of Simultaneous Nitrofuran (NF) and Chloramphenicol (CAP) Analytical Methods for AOAC Validation Study
Comparison of Simultaneous Nitrofuran (NF) and Chloramphenicol (CAP) Analytical Methods for AOAC Validation Study Haejung An Pacific Regional Lab-Southwest, FDA, Irvine, CA Three NF/CAP Methods Published
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 information