Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 1
`
`

`

`Fundamentals of
`Analytical
`Chemistry
`
`ninth Edition
`
`Douglas A. Skoog
`Stanford University
`
`Donald M. West
`San Jose State University
`
`F. James Holler
`University of Kentucky
`
`Stanley R. Crouch
`Michigan State University
`
`Australia • Brazil • Japan • Korea • Mexico • Singapore • Spain • United Kingdom • United States
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 2
`
`

`

`Fundamentals of Analytical Chemistry,
`Ninth Edition
`Douglas A. Skoog, Donald M. West, F. James
`Holler, Stanley R. Crouch
`
`Publisher: Mary Finch
`Acquisitions Editor: Chris Simpson
`Developmental Editor: Sandra Kiselica
`Assistant Editor: Alicia Landsberg
`Media Editor: Rebecca Berardy Schwartz
`Brand Manager: Nicole Hamm
`Market Development Manager:
`Janet del Mundo
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`PreMediaGlobal
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`Nesbitt Graphics; PreMediaGlobal
`Text and Cover Designer: Bill Reuter
`Cover Image: John F. Barry
`Interior Design Image: John F. Barry
`
`© 2014, 2004 Brooks/Cole, Cengage Learning
`
`ALL RIGHTS RESERVED. No part of this work covered by the copyright herein
`may be reproduced, transmitted, stored or used in any form or by any means
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`Section 107 or 108 of the 1976 United States Copyright Act, without the prior
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`
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`Cengage Learning Customer & Sales Support, 1-800-354-9706
`For permission to use material from this text or product,
`submit all requests online at www.cengage.com/permissions
`Further permissions questions can be emailed to
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`Library of Congress Control Number: 2012949970
`
`ISBN-13: 978-0-495-55828-6
`
`ISBN-10: 0-495-55828-1
`
`Brooks/Cole
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`USA
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`Printed in the United States of America
`1 2 3 4 5 6 7 16 15 14 13 12
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 3
`
`

`

`Contents in Brief
`
`Chapter 1
`The Nature of Analytical Chemistry 1
`Part I Tools of AnAlyTicAl chemisTry 14
`Chapter 2
`Chemicals, Apparatus, and Unit Operations of
`Analytical Chemistry 15
`Chapter 3
`Using Spreadsheets in Analytical Chemistry 48
`Chapter 4
`Calculations Used in Analytical Chemistry 62
`Chapter 5
`Errors in Chemical Analyses 82
`Chapter 6
`Random Errors in Chemical Analysis 93
`Chapter 7
`Statistical Data Treatment and Evaluation 123
`Chapter 8
`Sampling, Standardization, and Calibration 153
`Part II chemicAl equilibriA 196
`Chapter 9
`Aqueous Solutions and Chemical Equilibria 197
`Chapter 10
`Effect of Electrolytes on Chemical Equilibria 235
`Chapter 11
`Solving Equilibrium Problems for
`Complex Systems 249
`Part III clAssicAl meThods of AnAlysis 279
`Chapter 12 Gravimetric Methods of Analysis 280
`Chapter 13 Titrations in Analytical Chemistry 302
`Principles of Neutralization Titrations 322
`Chapter 14
`Chapter 15 Complex Acid/Base Systems 348
`Chapter 16 Applications of Neutralization Titrations 381
`Chapter 17 Complexation and Precipitation Reactions
`and Titrations 400
`Part IV elecTrochemicAl meThods 441
`Introduction to Electrochemistry 442
`Chapter 18
`Chapter 19 Applications of Standard Electrode Potentials 473
`Chapter 20 Applications of Oxidation/Reduction Titrations 509
`Potentiometry 535
`Chapter 21
`Bulk Electrolysis: Electrogravimetry and Coulometry 578
`Chapter 22
`Chapter 23 Voltammetry 610
`Part V specTrochemicAl meThods 649
`Introduction to Spectrochemical Methods 650
`Chapter 24
`Instruments for Optical Spectrometry 683
`Chapter 25
`Chapter 26 Molecular Absorption Spectrometry 722
`Chapter 27 Molecular Fluorescence Spectroscopy 760
`Chapter 28 Atomic Spectroscopy 773
`Chapter 29 Mass Spectrometry 802
`
`   iii
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 4
`
`

`

`iv  ContentsinBrief
`
`Part VI KineTics And sepArATions 818
`Chapter 30 Kinetic Methods of Analysis 819
`Chapter 31
`Introduction to Analytical Separations 847
`Chapter 32 Gas Chromatography 887
`Chapter 33 High-Performance Liquid Chromatography 912
`Chapter 34 Miscellaneous Separation Methods 935
`Part VII prAcTicAl AspecTs of chemicAl AnAlysis 959
`Part VII chapters are only available as an Adobe Acrobat® PDF file on the web at
`www.cengage.com/chemistry/skoog/fac9.
`
`Chapter 35 The Analysis of Real Samples 960
`Chapter 36
`Preparing Samples for Analysis 970
`Chapter 37 Decomposing and Dissolving the Sample 976
`Chapter 38
`Selected Methods of Analysis 986
`
`Glossary G-1
`
`Appendix 1 The Literature of Analytical Chemistry A-1
`Appendix 2
`Solubility Product Constants at 25°C A-6
`Appendix 3 Acid Dissociation Constants at 25°C A-8
`Appendix 4
`Formation Constants at 25°C A-10
`Appendix 5
`Standard and Formal Electrode Potentials A-12
`Appendix 6 Use of Exponential Numbers and Logarithms A-15
`Appendix 7 Volumetric Calculations Using Normality and Equivalent
`Weight A-19
`Appendix 8 Compounds Recommended for the Preparation of Standard
`Solutions of Some Common Elements A-27
`Appendix 9 Derivation of Error Propagation Equations A-29
`
`Answers to Selected Questions and Problems A-34
`I-1
`Index
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 5
`
`

`

`Contents
`
`Chapter 1 The Nature of Analytical Chemistry 1
`1A The Role of Analytical Chemistry 2
`1B Quantitative Analytical Methods 4
`1C A Typical Quantitative Analysis 4
`1D An Integral Role for Chemical Analysis:
`Feedback Control Systems 9
`Feature 1-1 Deer Kill: A Case Study Illustrating the Use
`of Analytical Chemistry to Solve a Problem
`in Toxicology 10
`Part I Tools of AnAlyTicAl
`chemisTry 14
`Chapter 2 Chemicals, Apparatus, and Unit Operations of
`Analytical Chemistry 15
`2A Selecting and Handling Reagents
`and Other Chemicals 16
`2B Cleaning and Marking
`of Laboratory Ware 17
`2C Evaporating Liquids 18
`2D Measuring Mass 18
`2E Equipment and Manipulations
`Associated with Weighing 25
`2F Filtration and Ignition of Solids 28
`2G Measuring Volume 34
`2H Calibrating Volumetric Glassware 43
`2I The Laboratory Notebook 45
`2J Safety in the Laboratory 46
`
`Chapter 3 Using Spreadsheets in
`Analytical Chemistry 48
`3A Keeping Records and Making Calculations 49
`3B More Complex Examples 52
`
`Chapter 4 Calculations Used
`in Analytical Chemistry 62
`4A Some Important Units of Measurement 62
`Feature 4-1 Unified Atomic Mass Units and the Mole 65
`Feature 4-2 The Factor-Label Approach
`to Example 4-2 67
`4B Solutions and Their Concentrations 67
`4C Chemical Stoichiometry 75
`
`Chapter 5 Errors in Chemical Analyses 82
`5A Some Important Terms 84
`5B Systematic Errors 87
`
`Chapter 6 Random Errors in Chemical Analysis 93
`6A The Nature of Random Errors 93
`Feature 6-1 Flipping Coins: A Student Activity to Illustrate a
`Normal Distribution 97
`6B Statistical Treatment of Random Errors 98
`Feature 6-2 Calculating the Areas under the Gaussian
`Curve 101
`Feature 6-3 The Significance of the Number of Degrees of
`Freedom 104
`Feature 6-4 Equation for Calculating the Pooled Standard
`Deviation 107
`6C Standard Deviation of Calculated Results 110
`6D Reporting Computed Data 115
`
`Chapter 7 Statistical Data Treatment and Evaluation 123
`7A Confidence Intervals 124
`Feature 7-1 W. S. Gossett (“Student”) 127
`7B Statistical Aids to Hypothesis Testing 129
`7C Analysis of Variance 140
`7D Detection of Gross Errors 146
`
`Chapter 8 Sampling, Standardization,
`and Calibration 153
`8A Analytical Samples and Methods 153
`8B Sampling 156
`8C Automated Sample Handling 164
`8D Standardization and Calibration 167
`Feature 8-1 Lab-on-a-Chip 168
`Feature 8-2 A Comparison Method for Aflatoxins 169
`Feature 8-3 Multivariate Calibration 180
`8E Figures of Merit for Analytical Methods 186
`Part II chemicAl equilibriA 196
`Chapter 9 Aqueous Solutions and Chemical
`Equilibria 197
`9A The Chemical Composition of Aqueous Solutions 197
`9B Chemical Equilibrium 202
`Feature 9-1 Stepwise and Overall Formation Constants for
`Complex Ions 205
`Feature 9-2 Why [H2O] Does Not Appear in Equilibrium-
`Constant Expressions for Aqueous Solutions 206
`Feature 9-3 Relative Strengths of Conjugate Acid/Base Pairs 212
`Feature 9-4 The Method of Successive Approximations 217
`9C Buffer Solutions 219
`
`   v
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 6
`
`

`

`vi  Contents
`
`Feature 9-5 The Henderson-Hasselbalch Equation 221
`Feature 9-6 Acid Rain and the Buffer Capacity of Lakes 227
`
`Chapter 10 Effect of Electrolytes on Chemical
`Equilibria 235
`10A The Effect of Electrolytes on Chemical Equilibria 235
`10B Activity Coefficients 239
`Feature 10-1 Mean Activity Coefficients 242
`
`Chapter 11 Solving Equilibrium Problems for Complex
`Systems 249
`11A Solving Multiple-Equilibrium Problems Using a
`Systematic Method 250
`11B Calculating Solubilities by the Systematic Method 256
`Feature 11-1 Algebraic Expressions Needed to Calculate the
` Solubility of CaC2O4 in Water 262
`11C Separation of Ions by Control of the Concentration of the
`Precipitating Agent 268
`Feature 11-2 Immunoassay: Equilibria in the Specific
` Determination of Drugs 272
`
`Part III clAssicAl meThods
`of AnAlysis 279
`Chapter 12 Gravimetric Methods of Analysis 280
`12A Precipitation Gravimetry 280
`Feature 12-1 Specific Surface Area of Colloids 287
`12B Calculation of Results from Gravimetric Data 291
`12C Applications of Gravimetric Methods 294
`
`Chapter 13 Titrations in Analytical Chemistry 302
`13A Some Terms Used in Volumetric Titrations 303
`13B Standard Solutions 305
`13C Volumetric Calculations 306
`Feature 13-1 Another Approach to Example 13-6(a) 311
`Feature 13-2 Rounding the Answer to Example 13-7 312
`13D Gravimetric Titrations 314
`13E Titration Curves 315
`Feature 13-3 Calculating the NaOH Volumes Shown in the First
`Column of Table 13-1 317
`
`Chapter 14 Principles of Neutralization Titrations 322
`14A Solutions and Indicators for Acid/Base Titrations 322
`14B Titration of Strong Acids and Bases 326
`Feature 14-1 Using the Charge-balance Equation to Construct
`Titration Curves 328
`Feature 14-2 Significant Figures in Titration Curve
`Calculations 331
`14C Titration Curves for Weak Acids 332
`Feature 14-3 Determining Dissociation Constants of Weak Acids
`and Bases 334
`Feature 14-4 A Master Equation Approach to Weak Acid/Strong
`Base Titrations 336
`14D Titration Curves for Weak Bases 337
`Feature 14-5 Determining the pK Values for Amino Acids 339
`14E The Composition of Solutions During Acid/Base
`Titrations 341
`Feature 14-6 Locating Titration End Points from
`pH Measurements 342
`
`Chapter 15 Complex Acid/Base Systems 348
`15A Mixtures of Strong and Weak Acids or Strong and
`Weak Bases 348
`15B Polyfunctional Acids and Bases 352
`15C Buffer Solutions Involving Polyprotic Acids 354
`15D Calculation of the pH of Solutions of NaHA 356
`15E Titration Curves for Polyfunctional Acids 360
`Feature 15-1 The Dissociation of Sulfuric Acid 368
`15F Titration Curves for Polyfunctional Bases 369
`15G Titration Curves for Amphiprotic Species 371
`Feature 15-2 Acid/Base Behavior of Amino Acids 371
`15H Composition of Polyprotic Acid Solutions as a Function
`of pH 373
`Feature 15-3 A General Expression for Alpha Values 374
`Feature 15-4 Logarithmic Concentration Diagrams 375
`
`Chapter 16 Applications of Neutralization Titrations 381
`16A Reagents for Neutralization Titrations 382
`16B Typical Applications of Neutralization Titrations 387
`Feature 16-1 Determining Total Serum Protein 388
`Feature 16-2 Other Methods for Determining
`Organic Nitrogen 388
`Feature 16-3 Equivalent Masses of Acids and Bases 394
`
`Chapter 17 Complexation and Precipitation Reactions
`and Titrations 400
`17A The Formation of Complexes 400
`Feature 17-1 Calculation of Alpha Values for Metal
`Complexes 403
`17B Titrations with Inorganic Complexing Agents 406
`Feature 17-2 Determination of Hydrogen Cyanide in
` Acrylonitrile Plant Streams 407
`17C Organic Complexing Agents 413
`17D Aminocarboxylic Acid Titrations 414
`Feature 17-3 Species Present in a Solution of EDTA 415
`Feature 17-4 EDTA as a Preservative 418
`Feature 17-5 EDTA Titration Curves When a Complexing Agent
`Is Present 428
`Feature 17-6 Enhancing the Selectivity of EDTA Titrations with
`Masking and Demasking Agents 435
`Feature 17-7 Test Kits for Water Hardness 436
`Part IV elecTrochemicAl
`meThods 441
`Chapter 18 Introduction to Electrochemistry 442
`18A Characterizing Oxidation/Reduction Reactions 442
`Feature 18-1 Balancing Redox Equations 444
`18B Electrochemical Cells 446
`Feature 18-2 The Daniell Gravity Cell 450
`18C Electrode Potentials 451
`Feature 18-3 Why We Cannot Measure Absolute Electrode
`Potentials 456
`Feature 18-4 Sign Conventions in the Older Literature 464
`Feature 18-5 Why Are There Two Electrode Potentials for Br2 in
`Table 18-1? 466
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 7
`
`

`

`Chapter 19 Applications of Standard Electrode
`Potentials 473
`19A Calculating Potentials of Electrochemical Cells 473
`19B Determining Standard Potentials Experimentally 480
`Feature 19-1 Biological Redox Systems 482
`19C Calculating Redox Equilibrium Constants 482
`Feature 19-2 A General Expression for Calculating Equilibrium
`Constants from Standard Potentials 487
`19D Constructing Redox Titration Curves 488
`Feature 19-3 The Inverse Master Equation Approach for Redox
`Titration Curves 497
`Feature 19-4 Reaction Rates and Electrode Potentials 502
`19E Oxidation/Reduction Indicators 502
`19F Potentiometric End Points 505
`
`Chapter 20 Applications of Oxidation/Reduction
`Titrations 509
`20A Auxiliary Oxidizing and Reducing Reagents 509
`20B Applying Standard Reducing Agents 511
`20C Applying Standard Oxidizing Agents 515
`Feature 20-1 Determination of Chromium Species in Water
`Samples 517
`Feature 20-2 Antioxidants 522
`
`Chapter 21 Potentiometry 535
`21A General Principles 536
`21B Reference Electrodes 537
`21C Liquid-Junction Potentials 539
`21D Indicator Electrodes 540
`Feature 21-1 An Easily Constructed Liquid-Membrane
` Ion-Selective Electrode 552
`Feature 21-2 The Structure and Performance of Ion-Sensitive
`Field Effect Transistors 554
`Feature 21-3 Point-of-Care Testing: Blood Gases, and Blood
`Electrolytes with Portable Instrumentation 558
`21E Instruments for Measuring Cell Potential 560
`Feature 21-4 The Loading Error in Potential
`Measurements 560
`Feature 21-5 Operational Amplifier Voltage Measurements 562
`21F Direct Potentiometry 563
`21G Potentiometric Titrations 569
`21H Potentiometric Determination of Equilibrium
`Constants 573
`
`Chapter 22 Bulk Electrolysis: Electrogravimetry and
`Coulometry 578
`22A The Effect of Current on Cell Potential 579
`Feature 22-1 Overvoltage and the Lead/Acid Battery 586
`22B The Selectivity of Electrolytic Methods 586
`22C Electrogravimetric Methods 588
`22D Coulometric Methods 594
`Feature 22-2 Coulometric Titration of Chloride in
`Biological Fluids 603
`
`Chapter 23 Voltammetry 610
`23A Excitation Signals in Voltammetry 611
`23B Voltammetric Instrumentation 612
`
`Contents  vii
`
`Feature 23-1 Voltammetric Instruments Based on Operational
`Amplifiers 613
`23C Hydrodynamic Voltammetry 618
`23D Polarography 633
`23E Cyclic Voltammetry 635
`23F Pulse Voltammetry 639
`23G Applications of Voltammetry 642
`23H Stripping Methods 643
`23I Voltammetry with Microelectrodes 645
`Part V specTrochemicAl AnAlysis 649
`Chapter 24 Introduction to Spectrochemical
`Methods 650
`24A Properties of Electromagnetic Radiation 651
`24B Interaction of Radiation and Matter 654
`Feature 24-1 Spectroscopy and the Discovery of Elements 657
`24C Absorption of Radiation 658
`Feature 24-2 Deriving Beer’s Law 660
`Feature 24-3 Why Is a Red Solution Red? 665
`2D Emission of Electromagnetic Radiation 674
`
`Chapter 25 Instruments for Optical Spectrometry 683
`25A Instrument Components 683
`Feature 25-1 Laser Sources: The Light Fantastic 687
`Feature 25-2 Origin of Equation 25-1 693
`Feature 25-3 Producing Ruled and Holographic Gratings 695
`Feature 25-4 Basis of Equation 25-2 698
`Feature 25-5 Signals, Noise, and the Signal-to-Noise
`Ratio 700
`Feature 25-6 Measuring Photocurrents with Operational
`Amplifiers 708
`25B Ultraviolet/Visible Photometers and
`Spectrophotometers 710
`25C Infrared Spectrophotometers 713
`Feature 25-7 How Does a Fourier Transform Infrared
` Spectrometer Work? 715
`
`Chapter 26 Molecular Absorption Spectrometry 722
`26A Ultraviolet and Visible Molecular Absorption
`Spectroscopy 722
`26B Automated Photometric and Spectrophotometric
`Methods 744
`26C Infrared Absorption Spectroscopy 746
`Feature 26-1 Producing Spectra with an FTIR
`Spectrometer 751
`
`Chapter 27 Molecular Fluorescence Spectroscopy 760
`27A Theory of Molecular Fluorescence 760
`27B Effect of Concentration on Fluorescence Intensity 764
`27C Fluorescence Instrumentation 765
`27D Applications of Fluorescence Methods 766
`Feature 27-1 Use of Fluorescence Probes in Neurobiology:
` Probing the Enlightened 767
`27E Molecular Phosphorescence Spectroscopy 769
`27F Chemiluminescence Methods 770
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 8
`
`

`

`viii  Contents
`
`Chapter 28 Atomic Spectroscopy 773
`28A Origins of Atomic Spectra 774
`28B Production of Atoms and Ions 776
`28C Atomic Emission Spectrometry 786
`28D Atomic Absorption Spectrometry 790
`Feature 28-1 Determining Mercury by Cold-Vapor Atomic
` Absorption Spectroscopy 797
`28E Atomic Fluorescence Spectrometry 799
`
`Chapter 29 Mass Spectrometry 802
`29A Principles of Mass Spectrometry 802
`29B Mass Spectrometers 804
`29C Atomic Mass Spectrometry 808
`29D Molecular Mass Spectrometry 811
`Part VI KineTics And sepArATions 818
`Chapter 30 Kinetic Methods of Analysis 819
`30A Rates of Chemical Reactions 820
`Feature 30-1 Enzymes 827
`30B Determining Reaction Rates 833
`Feature 30-2 Fast Reactions and Stopped-Flow Mixing 833
`30C Applications of Kinetic Methods 840
`Feature 30-3 The Enzymatic Determination of Urea 842
`
`Chapter 31 Introduction to Analytical Separations 847
`31A Separation by Precipitation 848
`31B Separation of Species by Distillation 852
`31C Separation by Extraction 852
`Feature 31-1 Derivation of Equation 31-3 854
`31D Separating Ions by Ion Exchange 857
`Feature 31-2 Home Water Softeners 860
`31E Chromatographic Separations 861
`Feature 31-3 What Is the Source of the Terms Plate and
`Plate Height? 871
`Feature 31-4 Derivation of Equation 31-24 872
`
`Chapter 32 Gas Chromatography 887
`32A Instruments for Gas-Liquid Chromatography 888
`32B Gas Chromatographic Columns and Stationary Phases 897
`32C Applications of Gas-Liquid Chromatography 901
`Feature 32-1 Use of GC/MS to Identify a Drug Metabolite
`in Blood 903
`32D Gas-Solid Chromatography 909
`
`Chapter 33 High-Performance Liquid
`Chromatography 912
`33A Instrumentation 913
`Feature 33-1 LC/MS and LC/MS/MS 920
`33B Partition Chromatography 921
`33C Adsorption Chromatography 924
`33D Ion Chromatography 925
`33E Size-Exclusion Chromatography 927
`Feature 33-2 Buckyballs: The Chromatographic Separation
`of Fullerenes 929
`33F Affinity Chromatography 931
`33G Chiral Chromatography 931
`33H Comparison of High-Performance Liquid Chromatography
`and Gas Chromatography 932
`
`Chapter 34 Miscellaneous Separation Methods 935
`34A Supercritical Fluid Separations 935
`34B Planar Chromatography 940
`34C Capillary Electrophoresis 942
`Feature 34-1 Capillary Array Electrophoresis in DNA
`Sequencing 949
`34D Capillary Electrochromatography 949
`34E Field-Flow Fractionation 952
`Part VII prAcTicAl AspecTs
`of chemicAl AnAlysis 959
`The following chapters are available as Adobe Acrobat®
`PDF files at www.cengage.com/chemistry/skoog/fac9.
`
`Chapter 35 The Analysis of Real Samples 960
`35A Real Samples 960
`35B Choice of Analytical Method 962
`35C Accuracy in the Analysis of Complex Materials 967
`
`Chapter 36 Preparing Samples for Analysis 970
`36A Preparing Laboratory Samples 970
`36B Moisture in Samples 972
`36C Determining Water in Samples 975
`
`Chapter 37 Decomposing and Dissolving the
`Sample 976
`37A Sources of Error in Decomposition and
`Dissolution 977
`37B Decomposing Samples with Inorganic Acids in
`Open Vessels 977
`37C Microwave Decompositions 979
`37D Combustion Methods for Decomposing Organic
`Samples 982
`37E Decomposing Inorganic Materials with Fluxes 984
`
`Chapter 38 Selected Methods of Analysis 986
`38A An Introductory Experiment 987
`38B Gravimetric Methods of Analysis 996
`38C Neutralization Titrations 1000
`38D Precipitation Titrations 1009
`38E Complex-Formation Titrations with EDTA 1012
`38F Titrations with Potassium Permanganate 1015
`38G Titrations with Iodine 1021
`38H Titrations with Sodium Thiosulfate 1023
`38I Titrations with Potassium Bromate 1026
`38J Potentiometric Methods 1028
`38K Electrogravimetric Methods 1032
`38L Coulometric Titrations 1034
`38M Voltammetry 1036
`38N Methods Based on the Absorption of Radiation 1038
`38O Molecular Fluorescence 1042
`38P Atomic Spectroscopy 1043
`38Q Application of Ion-Exchange Resins 1046
`38R Gas-Liquid Chromatography 1048
`
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`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 9
`
`

`

`Contents  ix
`
`Glossary G-1
`Appendix 1 The Literature of Analytical Chemistry A-1
`Appendix 2 Solubility Product Constants at 25°C A-6
`Appendix 3 Acid Dissociation Constants at 25°C A-8
`Appendix 4 Formation Constants at 25°C A-10
`Appendix 5 Standard and Formal Electrode
`Potentials A-12
`Appendix 6 Use of Exponential Numbers and
`Logarithms A-15
`
`Appendix 7 Volumetric Calculations Using Normality and
`Equivalent Weight A-19
`Appendix 8 Compounds Recommended for the
`Preparation of Standard Solutions of Some
`Common Elements A-27
`Appendix 9 Derivation of Error Propagation
`Equations A-29
`Answers to Selected Questions and Problems A-34
`
`Index I-1
`
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`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
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`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 10
`
`

`

`Appendix 9
`
`Derivation of Error Propagation Equations
`
`In this appendix, we derive several equations that permit the calculation of the standard
`deviation for the results from various types of arithmetical computations.
`
`A9A ProPAgAtion of MeAsureMent uncertAinties
`The calculated result for a typical analysis ordinarily requires data from several indepen-
`dent experimental measurements, each of which is subject to a random uncertainty and
`each of which contributes to the net random error of the final result. For the purpose of
`showing how such random uncertainties affect the outcome of an analysis, let us assume
`that a result y is dependent on the experimental variables, a, b, c, . . ., each of which fluc-
`tuates in a random and independent way. In other words, y is a function of a, b, c, . . ., so
`we may write
`
`
`
`y  f ( a, b, c, . . .)
`
`(A9-1)
`
`The uncertainty dyi is generally given in terms of the deviation from the mean or
`(yi  y), which will depend on the size and sign of the corresponding uncertainties
`dai, dbi, dci, . . . . Thus,
`
`dyi  (yi  y)  f ( dai, dbi, dci, . . .)
`
`The uncertainty in dy as a function of the uncertainties in a, b, c, . . . can be derived by
`taking the total differential of Equation A9-1. Therefore,
`
`b,c, . . .
`
`a,c, . . .
`
`dc  . . .
`a,b, . . .
`
`(A9-2)
`
`To develop a relationship between the standard deviation of y and the standard deviations
`of a, b, and c for N replicate measurements, we employ Equation 6-4 (p. 103), which
`requires that we square Equation A9-2, sum between i  0 and i  N, divide by N  1,
`and take the square root of the result. The square of Equation A9-2 takes the form
`
`This equation must then be summed between the limits of i  1 to i  N.
`In squaring Equation A9-2, two types of terms emerge from the right-hand side of the
`equation: (1) square terms and (2) cross terms. Square terms take the form
`
`dc  . . . d 2
`
`a,b., . . .
`
`
`
`(A9-3)
`
` dc2, . . .
`
`  A-29
`
`'ab
`dy  a 'y
`'ab
`(dy)2  ca 'y
`
`
`
`
`
`'bb
`da  a 'y
`'bb
`da  a 'y
`'ab2
`'bb2
`a 'y
` da2, a 'y
`
`b,c, . . .
`
`a,c, . . .
`
`'cb
`db  a'y
`'cb
`db  a'y
`'cb2
` db2, a'y
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 11
`
`

`

`A-30  Appendix 9
`
`derivation of error propagation equations
`
`Square terms are always positive and can, therefore, never cancel when summed. In con-
`trast, cross terms may be either positive or negative in sign. Examples are
`
`If da, db, and dc represent independent and random uncertainties, some of the cross terms
`will be negative and others positive. Thus, the sum of all such terms should approach zero,
`particularly when N is large.
`As a consequence of the tendency of cross terms to cancel, the sum of Equation A9-3
`from i  1 to i  N can be assumed to be made up exclusively of square terms. This sum
`then takes the form
`
`'cb dadc, . . .a 'y'ab a 'y'bb dadb, a 'y'ab a'y
`
`
`
`
`  (dai)2  a 'y
`  (dbi)2  a'y
`'bb2
`'cb2
`a 'y
`a'y
`'bb2
`'cb2
`
`  (dci)2  . . .
`
`(A9-4)
`
` (dai)2
`N  1
`
`
`
` (dbi)2
`N  1
`
`
`
` (dci)2
`N  1
`
`
`
` c
`
`(A9-5)
`
` (dyi)2  a 'y
`'ab2
`a 'y
`'ab2
`
` (dyi)2
`N  1
`
`
`
`
`
`Dividing through by N  1 gives
`
`From Equation 6-4, however, we see that
`
` (dyi)2
`N  1
`
` 
`
`(yi  y)2
`N  1
`
`2
` sy
`
`2 is the variance of y. Similarly,
`where sy
`
` (dai)2
`N  1
`
`
`
`(ai  a)2
`N  1
`
`2
` sa
`
`and so forth. Thus, Equation A9-5 can be written in terms of the variances of the
` variables, that is,
`
`2  a 'y
`'ab2
`
`sy
`
`2  a 'y
`'bb2
`
` sa
`
`2  a'y
`'cb2
`
` sb
`
`
`
`2  . . .
`sc
`
`(A9-6)
`
`A9B the stAndArd deviAtion of coMPuted results
`In this section, we employ Equation A9-6 to derive relationships that permit calculation
`of standard deviations for the results produced by five types of arithmetic operations.
`A9B-1 Addition and Subtraction
`Consider the case where we wish to compute the quantity y from the three experimental
`quantities a, b, and c by means of the equation
`
`y  a  b  c
`
`Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has
`deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
`
`Opiant Exhibit 2219
`Nalox