Analytical Techniques for Clinical Chemistry: Methods and Applications -- CONTENTS -- FOREWORD -- PREFACE -- CONTRIBUTORS -- PART I: Exploring Fundamentals -- 1. Good Clinical Practice Principles: Legal Background and Applicability -- Summary -- 1.1. Introduction -- 1.2. Good Clinical Practice -- 1.2.1. ICH E6: Guidelines for Good Clinical Practice -- 1.2.2. WHO Guidelines for Good Clinical Practice for Trials on Pharmaceutical Products -- 1.2.3. WHO Handbook for Good Clinical Research Practice Guidance for Implementation -- 1.2.4. WHO Good Clinical Laboratory Practice -- 1.3. Good Clinical Practice: Legal Background in the European Union -- 1.4. Good Clinical Practice: Applicability in the European Union -- 1.4.1. EU 2007 Conference on the Implementation and Applicability in the European Union of Legislation on Clinical Trials of Medical Products -- 1.4.2. Directives 2001/20/EC, 2005/28/EC, and Good Clinical Practice in Case of Noncommercial Clinical Trials -- 1.5. Good Clinical Practice and Bioequivalence Trials: GCP Inspections and Laboratories -- 1.5.1. General Aspects -- 1.5.2. EMA Guidelines on Bioequivalence Studies -- 1.5.3. EMA Reflection Paper for Applicants Who Want to Submit Bioequivalence Performed Outside the European Union -- 1.5.4. Good Clinical Practice Bioequivalence Inspections -- 1.5.5. Good Clinical Practice Clinical Laboratory Inspections -- 1.5.6. Good Clinical Practice Inspections on Phase I Units -- 1.6. Good Clinical Practice for Clinical Trials with Advanced Therapy Medicinal Product -- 1.7. Good Clinical Practice and Clinical Trials in Developing Countries -- 1.7.1. The Increase of Clinical Trials in Developing Countries -- 1.7.2. European Union Legislation and Clinical Trials in Developing Countries -- References -- 2. Clinical Chemistry and the Quest for Quality -- Summary -- 2.1. Introduction -- 2.2. Quality Today.

2.2.1. General Aspects -- 2.2.2. Major Quality Systems and Their Scope -- 2.3. Conclusions -- References -- 3. Uncertainty in Clinical Chemistry Measurements Including Preanalytical Variables -- Summary -- 3.1. Introduction -- 3.2. Analytical Uncertainty in Laboratory Results -- 3.2.1. General Aspects -- 3.2.2. Control Materials -- 3.2.3. Estimating Analytical Precision -- 3.2.4. Within-Run Precision (Repeatability) -- 3.2.5. Total Analytical Precision (Reproducibility) -- 3.2.6. Estimating Precision Using Duplicates -- 3.3. Trueness and Traceability -- 3.3.1. Basic Concepts -- 3.3.2. Reference Methods and Materials -- 3.3.3. Estimating the Trueness -- 3.3.4. Factorizing the Patients' Results -- 3.3.5. Changing Reagent Lot -- 3.3.6. Analytical Specificity -- 3.3.7. Method Validation -- 3.4. Proficiency Testing -- 3.4.1. Background Information -- 3.4.2. Choice of EQA Schemes -- 3.4.3. Interpretation and Actions -- 3.5. Biological Variations and Quality Goals -- 3.6. Reference Intervals -- 3.6.1. Establishing Reference Intervals -- 3.6.2. Transferring Reference Intervals -- 3.7. Estimating Preanalytical Uncertainty -- 3.7.1. Setting the Stage -- 3.7.2. Preanalytical Variables -- 3.7.3. The Model for an Uncertainty Budget -- 3.7.4. Statistical Analysis -- 3.7.5. Assumptions and Modeling Details -- 3.8. Conclusions -- References -- 4. The Role and Significance of Reference Values in the Identification and Evaluation of Trace Elements from Diet -- Summary -- 4.1. Reference Values -- 4.2. Reference Values in Specific Groups of Population: The Children Case -- 4.3. Trace Elements and Diet -- 4.4. Arsenic -- 4.5. Mercury -- 4.6. Lead -- 4.7. Chromium -- 4.8. Cadmium -- 4.9. Conclusions -- References -- 5. Sample Collection, Storage, and Pretreatment in Clinical Chemistry -- Summary -- 5.1. Introduction -- 5.2. Collection Procedures -- 5.2.1. Sample Types.

5.2.2. Practical Issues -- 5.3. Storage -- 5.4. Pretreatment -- 5.5. Conclusions -- References -- 6. Metal Toxicology in Clinical, Forensic, and Chemical Pathology -- Summary -- 6.1. Introduction -- 6.2. Biological Markers -- 6.3. Methodology for Trace Metal Ion Analysis in Clinical, Forensic, and Chemical Pathology -- 6.3.1. Clinical Chemistry Implications -- 6.3.2. Forensic Toxicology Implications -- 6.3.3. Chemical Pathology Implications -- 6.4. Case Studies of Relevance to Research and Diagnosis on Clinical Chemistry, Forensic Toxicology, and Chemical Pathology -- 6.4.1. Case Study No. 1: Copper Levels in Placental Tissues as a Biomarker for Menkes Disease -- 6.4.2. Case Study No. 2: Cd, Fe, Se, and Zn in Prostate Tissue as Biomarkers for Prostate Disease -- 6.4.3. Case Study No. 3: Measurement of Dental Implant Corrosion Products and Histological Correlation in Periimplant Tissues -- 6.4.4. Case Study No. 4: Skin Pigmentation after Exposure to Topical Hg from Skin Ointment -- 6.4.5. Case Study No. 5: Analysis of U Isotope Ratios by using ICP-MS for the Assessment of Natural U or DU Exposures -- Disclaimer -- References -- PART II: Selected Applications -- 7. Elemental Speciation in Clinical Sciences -- Summary -- 7.1. Introduction -- 7.1.1. General Aspects -- 7.1.2. Definitions -- 7.1.3. Levels of Speciation -- 7.2. Selected Elements -- 7.2.1. Background Concepts -- 7.2.2. Biological Speciation of Essential Elements -- 7.2.3. Biological Speciation of Toxic Elements -- 7.3. Conclusions -- References -- 8. The Role of Analytical Chemistry in the Safety of Drug Therapy -- Summary -- 8.1. Drug Quality and Analysis: Their Role in Drug Safety -- 8.1.1. Introductory Remarks -- 8.1.2. The Role of Pharmacopoeias in Assuring Drug Quality -- 8.2. Methodological Aspects -- 8.2.1. Historical Overview -- 8.2.2. Spectroscopic Techniques.

8.2.3. Chromatography and Related Techniques -- 8.2.4. Hyphenated Techniques -- 8.2.5. Miscellaneous Methods -- 8.3. The Role of Analytical Chemistry in Drug Research, Development, and Production -- 8.3.1. QC of Drugs -- 8.3.2. Drug Impurity Profiling -- 8.3.3. Drug Stability Issues -- 8.3.4. Contribution of Analytical Chemistry to Drug Research -- 8.3.5. Chiral Issues -- 8.4. Future Trends -- References -- 9. Analytical Techniques and Quality Control of Pharmaceuticals -- Summary -- 9.1. Introduction -- 9.2. Sources of Impurities in Medicines -- 9.3. Validation of Analytical Methods -- 9.3.1. Specificity -- 9.3.2. Linearity -- 9.3.3. Precision -- 9.3.4. Trueness -- 9.3.5. Accuracy -- 9.3.6. Dosing Range -- 9.3.7. Quantification Limit -- 9.4. Analytical Approaches -- 9.4.1. General -- 9.4.2. TLC -- 9.4.3. HPLC -- 9.4.4. CE -- 9.5. Conclusions -- References -- 10. Detection of Drugs in Biological Fluids for Antidoping Control -- Summary -- 10.1. Introduction -- 10.2. Doping Control and Analytical Requirements -- 10.3. Confirmation Techniques -- 10.4. Conclusions -- References -- 11. The Applicability of Plasma-Based Techniques to Biological Monitoring -- Summary -- 11.1. Introduction -- 11.2. ICP as a Spectrochemical Source -- 11.3. Element Analysis in Environmental and Biological Materials -- 11.3.1. General -- 11.3.2. Method Development -- 11.3.3. Reference Materials -- 11.3.4. Environmental Applications -- 11.3.5. Studies on Human Subjects -- 11.3.6. Studies on Animals -- 11.3.7. Studies on Drugs -- 11.3.8. Studies on Food -- 11.4. Conclusions -- References -- 12. Atomic Spectrometric Techniques for the Analysis of Clinical Samples -- Summary -- 12.1. Introduction -- 12.2. Analytical Techniques -- 12.2.1. Atomic Absorption Spectrometry -- 12.2.2. Atomic Emission Spectrometry -- 12.2.3. Atomic Fluorescence Spectrometry.

12.2.4. Inductively Coupled Plasma Mass Spectrometry -- 12.2.5. State of the Art -- 12.3. Sample Preparation -- 12.3.1. Precautions During Sampling and Contamination Control -- 12.3.2. Storage of Samples -- 12.3.3. Methods for Sample Preparation -- 12.3.4. Direct Analysis of Solid Samples -- 12.4. Speciation Analysis -- 12.5. Quality Control in Trace Element Determination -- 12.6. Conclusions -- References -- 13. Applications of ICP-MS in Human Biomonitoring Studies -- Summary -- 13.1. Introduction -- 13.2. Advantages and Limitations of Inductively Coupled Plasma Mass Spectrometry -- 13.3. Sample Collection and Storage -- 13.4. Sample Preparation -- 13.5. Human Biomonitoring by Inductively Coupled Plasma Mass Spectrometry -- 13.5.1. General -- 13.5.2. Potentially Toxic Elements: Cadmium, Mercury, Lead -- 13.5.3. Essential Trace Elements: Copper, Selenium, Zinc -- 13.5.4. Nonmetals: Bromine and Iodine -- 13.5.5. Precious Metals: Silver, Gold, Iridium, Palladium, and Platinum -- 13.5.6. Actinides: Uranium and Thorium -- 13.5.7. Multielemental Determinations -- 13.6. Trace Element Speciation and Metallomics -- 13.7. Determination of Stable Isotopes -- 13.8. Method Validation and Quality Assurance -- 13.9. Conclusions -- References -- 14. Molybdenum in Biological Samples and Clinical Significance of Serum Molybdenum -- Summary -- 14.1. Introduction -- 14.2. Analysis of Molybdenum in Biological Samples by Inductively Coupled Plasma Mass Spectrometry -- 14.2.1. General -- 14.2.2. Sample Preparation -- 14.2.3. Determinations by Inductively Coupled Plasma Mass Spectrometry -- 14.3. Molybdenum in Food -- 14.3.1. Molybdenum Concentration in Food -- 14.3.2. Speciation of Molybdenum in Food -- 14.3.3. Molybdenum Intake in Human Population -- 14.4. Molybdenum in Human Samples -- 14.4.1. Molybdenum in Urine -- 14.4.2. Molybdenum in Blood.

14.4.3. Molybdenum in Milk.