Measuring elemental impurities in pharmaceuticals : a practical guide

503 Pages·2018·33.202 MB·English

by  Thomas, Robert

Measuring Elemental
Impurities in
Pharmaceuticals
A Practical Guide
PRACTICAL SPECTROSCOPY A SERIES
Infrared and Raman Spectroscopy (in three parts), edited by Edward G. Brame, Jr. and Jeanette G. Grasselli
X-Ray Spectrometry, edited by H. K. Herglotz and L. S. Birks
Mass Spectrometry (in two parts), edited by Charles Merritt, Jr. and Charles N. McEwen
Infrared and Raman Spectroscopy of Polymers, H. W. Siesler and K. Holland-Moritz
NMR Spectroscopy Techniques, edited by Cecil Dybowski and Robert L. Lichter
Infrared Microspectroscopy: Theory and Applications, edited by Robert G. Messerschmidt and Matthew
A. Harthcock
Flow Injection Atomic Spectroscopy, edited by Jose Luis Burguera
Mass Spectrometry of Biological Materials, edited by Charles N. McEwen and Barbara S. Larsen
Field Desorption Mass Spectrometry, László Prókai
Chromatography/Fourier Transform Infrared Spectroscopy and Its Applications, Robert White
Modern NMR Techniques and Their Application in Chemistry, edited by Alexander I. Popov and Klaas Hallenga
Luminescence Techniques in Chemical and Biochemical Analysis, edited by Willy R. G. Baeyens, Denis De
Keukeleire, and Katherine Korkidis
Handbook of Near-Infrared Analysis, edited by Donald A. Burns and Emil W. Ciurczak
Handbook of X-Ray Spectrometry: Methods and Techniques, edited by René E. Van Grieken and Andrzej
A. Markowicz
Internal Reflection Spectroscopy: Theory and Applications, edited by Francis M. Mirabella, Jr.
Microscopic and Spectroscopic Imaging of the Chemical State, edited by Michael D. Morris
Mathematical Analysis of Spectral Orthogonality, John H. Kalivas and Patrick M. Lang
Laser Spectroscopy: Techniques and Applications, E. Roland Menzel
Practical Guide to Infrared Microspectroscopy, edited by Howard J. Humecki
Quantitative X-ray Spectrometry: Second Edition, Ron Jenkins, R. W. Gould, and Dale Gedcke
NMR Spectroscopy Techniques: Second Edition, Revised and Expanded, edited by Martha D. Bruch
Spectrophotometric Reactions, Irena Nemcova, Ludmila Cermakova, and Jiri Gasparic
Inorganic Mass Spectrometry: Fundamentals and Applications, edited by Christopher M. Barshick, Douglas C.
Duckworth, and David H. Smith
Infrared and Raman Spectroscopy of Biological Materials, edited by Hans-Ulrich Gremlich and Bing Yan
Near-Infrared Applications In Biotechnology, edited by Ramesh Raghavachari
Ultrafast Infrared and Ramen Spectroscopy, edited by M. D. Fayer
Handbook of Near-Infrared Analysis: Second Edition, Revised and Expanded, edited by Donald A. Burns and Emil
W. Ciurczak
Handbook of Raman Spectroscopy: From the Research Laboratory to the Process Line, edited by Ian R. Lewis and
Howell G. M. Edwards
Handbook of X-Ray Spectrometry: Second Edition, Revised and Expanded, edited by René E. Van Grieken and
Andrzej A. Markowicz
Ultraviolet Spectroscopy and UV Lasers, edited by Prabhakar Misra and Mark A. Dubinskii
Pharmaceutical and Medical Applications of Near-Infrared Spectroscopy, Second Edition, Emil W. Ciurczak
and James K. Drennen III
Applied Electrospray Mass Spectrometry, edited by Birendra N. Pramanik, A. K. Ganguly, and Michael L. Gross
Practical Guide to ICP-MS, edited by Robert Thomas
NMR Spectroscopy of Biological Solids, edited by A. Ramamoorthy
Handbook of Near Infrared Analysis, Third Edition, edited by Donald A. Burns and Emil W. Ciurczak
Coherent Vibrational Dynamics, edited by Guglielmo Lanzani, Giulio Cerullo, and Sandro De Silvestri
Practical Guide to ICP-MS: A Tutorial for Beginners, Second Edition, Robert Thomas
Practical Guide to ICP-MS: A Tutorial for Beginners, Third Edition, Robert Thomas
Pharmaceutical and Medical Applications of Near-Infrared Spectroscopy, Emil W. Ciurczak and Benoit Igne
Measuring Elemental Impurities in Pharmaceuticals: A Practical Guide, Robert Thomas
Measuring Elemental
Impurities in
Pharmaceuticals
A Practical Guide
By
Robert Thomas
CRC Press
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Library of Congress Cataloging‑ in‑ Publication Data
Names: Thomas, Robert, 1949‑ author.
Title: Measuring elemental impurities in pharmaceuticals : a practical guide
/ Robert Thomas.
Other titles: Practical spectroscopy ; v. 40.
Description: Boca Raton : Taylor & Francis, 2018. | Series: Practical
spectroscopy ; [v. 40] | Includes bibliographical references and index.
Identifiers: LCCN 2017038198 | ISBN 9781138197961 (hardback : alk. paper)
Subjects: | MESH: Pharmaceutical Preparations‑‑analysis | Mass
Spectrometry‑‑methods | Drug Contamination | Metals, Heavy |
Pharmaceutical Preparations‑‑standards | Laboratory Manuals
Classification: LCC RM301 | NLM QV 25 | DDC 615.1‑‑dc23
LC record available at https://lccn.loc.gov/2017038198
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
Contents
Foreword ..................................................................................................................xv
Preface ...................................................................................................................xvii
Acknowledgment ...................................................................................................xxv
Author ..................................................................................................................xxvii
Chapter 1 Testing for Heavy Metals: An ACS Perspective ..................................1
Introduction ..........................................................................................1
What Is a Reagent Chemical? ..............................................................2
Historical Perspective ...........................................................................2
Eleventh Edition ...................................................................................3
Heavy Metals Test ................................................................................3
Sulfide Colorimetric and Precipitation Procedure ...............................4
Which Plasma‑Based Spectrochemical Technique Is the Best
One to Use? ..........................................................................................5
Optimum Technique Based on Detection Limits, Sensitivity,
and Linear Dynamic Range .................................................................6
Approaches to Reducing Interferences ................................................7
Calibration ............................................................................................8
Instrumentation ....................................................................................8
Measurement Procedure and Data Integrity ........................................9
Final Thoughts .....................................................................................9
Acknowledgments ..............................................................................10
References ..........................................................................................10
Chapter 2 Elemental Impurities in Pharmaceuticals: An Overview ..................11
Background ........................................................................................11
Beginnings of Change ........................................................................13
Development of New Limits and Procedure General Chapters .........14
General Chapter <232>, “Elemental Impurities—Limits”: Overview .....16
Application of Limits and Risk Assessment of Excipients and
Drug Substances .................................................................................17
Speciation ...........................................................................................17
Elemental Impurity Classes ...............................................................18
Exposure and Route of Administration ..............................................19
Options for Demonstrating Compliance ............................................20
Drug Product Option .....................................................................21
Summation Option ........................................................................21
Individual Component Option .......................................................21
Justification for Levels Higher than the PDE .....................................22
Risk Assessment and Regulatory Considerations ..............................23
General Chapter <233>, “Elemental Impurities—Procedures”:
Overview ............................................................................................24
v
vi Contents
USP <233> Compendial Procedures 1 and 2 ....................................24
Sample Preparation ........................................................................25
USP <233> J‑Value Parameter ......................................................25
Alternative Procedure Validation: USP <233> Requirements .....26
Limit Procedures: Detectability ....................................................26
Acceptance Criteria: Noninstrumental Procedures.......................27
Acceptance Criteria: Instrumental Procedures .............................27
Limit Procedures: Precision (Repeatability) and Specificity ........27
Quantitative Testing Validation Requirements ..............................27
Final Thoughts ...................................................................................28
References ..........................................................................................29
Chapter 3 An Overview of ICP: Mass Spectrometry .........................................31
Principles of Operation ......................................................................31
Chapter 4 Principles of Ion Formation ................................................................35
Ion Formation .....................................................................................35
Natural Isotopes .................................................................................37
Chapter 5 Sample Introduction ...........................................................................41
Aerosol Generation .............................................................................41
Droplet Selection ................................................................................43
Nebulizers ..........................................................................................44
Concentric Design .........................................................................45
Cross‑Flow Design ........................................................................45
Microflow Design ..........................................................................47
Spray Chambers .................................................................................48
Double‑Pass Spray Chamber .........................................................49
Cyclonic Spray Chamber ...............................................................49
Aerosol Dilution .................................................................................51
Final Thoughts ...................................................................................52
References ..........................................................................................52
Chapter 6 Plasma Source ....................................................................................53
Plasma Torch ......................................................................................54
Formation of an ICP Discharge ..........................................................57
Function of the RF Generator ............................................................57
Ionization of the Sample.....................................................................59
References ..........................................................................................60
Chapter 7 Interface Region .................................................................................61
Capacitive Coupling ...........................................................................63
Ion Kinetic Energy .............................................................................65
Benefits of a Well‑Designed Interface ................................................66
Contents vii
Final Thoughts ...................................................................................67
References ..........................................................................................67
Chapter 8 Ion‑Focusing System ..........................................................................69
Role of the Ion Optics .........................................................................69
Dynamics of Ion Flow ........................................................................71
Commercial Ion Optic Designs ..........................................................73
References ..........................................................................................77
Chapter 9 Mass Analyzers: Quadrupole Technology .........................................79
Quadrupole Technology .....................................................................80
Basic Principles of Operation .............................................................80
Quadrupole Performance Criteria ......................................................82
Resolution ......................................................................................83
Abundance Sensitivity ...................................................................84
Benefit of Good Abundance Sensitivity ........................................86
References ..........................................................................................87
Chapter 10 Mass Analyzers: Double‑Focusing Magnetic Sector Technology .....89
Magnetic Sector Mass Spectroscopy: A Historical Perspective ........89
Use of Magnetic Sector Technology for ICP‑MS ...............................90
Principles of Operation of Magnetic Sector Technology ...................91
Resolving Power ............................................................................92
Other Benefits of Magnetic Sector Instruments .................................95
Simultaneous Measurement Approach Using One Detector..............95
Final Thoughts ...................................................................................97
References ..........................................................................................97
Chapter 11 Mass Analyzers: Time‑of‑Flight Technology ...................................99
Basic Principles of TOF Technology..................................................99
Commercial Designs ........................................................................100
Differences Between Orthogonal and On‑Axis TOF .......................103
Benefits of TOF Technology for ICP‑MS .........................................104
Rapid Transient Peak Analysis ....................................................104
Improved Precision ......................................................................105
Rapid Data Acquisition................................................................105
High‑Speed MultiElemental Imaging .............................................106
Final Thoughts .................................................................................107
References ........................................................................................107
Chapter 12 Mass Analyzers: Collision/Reaction Cell and Interface
Technology ......................................................................................109
Basic Principles of Collision/Reaction Cells ...................................110
Different Collision/Reaction Cell Approaches ................................111
viii Contents
Collisional Mechanisms Using Nonreactive Gases and
Kinetic Energy Discrimination ...................................................112
Reaction Mechanisms with Highly Reactive Gases and
Discrimination by Selective Bandpass Mass Filtering ................116
Dynamic Reaction Cell ...............................................................116
Low‑Mass‑Cutoff Collision/Reaction Cell .................................120
Triple‑Quadrupole Collision/Reaction Cell ................................123
M/S Mode ....................................................................................124
MS/MS Mode ..............................................................................124
On‑Mass MS/MS Mode ..............................................................124
Mass‑Shift MS/MS Mode ...........................................................125
Integrated Collision/Reaction Cell ...................................................127
Using Reaction Mechanisms in a Collision Cell ..............................129
Universal Cell ...................................................................................132
Detection Limit Comparison ............................................................133
Final Thoughts .................................................................................134
References ........................................................................................135
Chapter 13 Ion Detectors ...................................................................................137
Channel Electron Multiplier .............................................................137
Faraday Cup .....................................................................................139
Discrete Dynode Electron Multiplier ...............................................139
Extending the Dynamic Range ........................................................140
Filtering the Ion Beam .................................................................140
Using Two Detectors ...................................................................140
Using Two Scans with One Detector ...........................................141
Using One Scan with One Detector ............................................142
Extending the Dynamic Range Using Pulse‑Only Mode ................144
Simultaneous Array Detectors .........................................................145
References ........................................................................................146
Chapter 14 Peak Measurement Protocol .............................................................147
Measurement Variables ....................................................................147
Measurement Protocol......................................................................148
Optimization of Measurement Protocol ...........................................152
Multielement Data Quality Objectives .............................................153
Data Quality Objectives for Single‑Particle Icp‑Ms Studies ...........158
Final Thoughts .................................................................................159
References ........................................................................................160
Chapter 15 Methods of Quantitation ..................................................................161
Quantitative Analysis .......................................................................161
External Standardization .............................................................162
Standard Additions ......................................................................163
Addition Calibration ....................................................................164
Contents ix
Semiquantitative Analysis ................................................................165
Isotope Dilution ................................................................................166
Isotope Ratios ...................................................................................169
Internal Standardization ...................................................................169
References ........................................................................................170
Chapter 16 Review of ICP‑MS Interferences ....................................................173
Spectral Interferences .......................................................................173
Oxides, Hydroxides, Hydrides, and Doubly Charged Species ....174
Isobaric Interferences ..................................................................175
Ways to Compensate for Spectral Interferences ..........................176
Mathematical Correction Equations .......................................176
Cool and Cold Plasma Technology .........................................178
Collision/Reaction Cells .........................................................180
High‑Resolution Mass Analyzers ...........................................181
Matrix Interferences .........................................................................182
Compensation Using Internal Standardization ...........................182
Space Charge–Induced Matrix Interferences ..............................183
References ........................................................................................184
Chapter 17 Routine Maintenance .......................................................................185
Sample Introduction System ............................................................186
Peristaltic Pump Tubing ..............................................................186
Nebulizers ....................................................................................187
Spray Chamber ............................................................................189
Plasma Torch ...............................................................................190
Interface Region ...............................................................................191
Ion Optics .........................................................................................193
Roughing Pumps ..............................................................................194
Air Filters .........................................................................................194
Other Components to Be Periodically Checked ..............................195
Detector .......................................................................................195
Turbomolecular Pumps................................................................195
Mass Analyzer and Collision/Reaction Cell ...............................196
Final Thoughts .................................................................................196
Reference ..........................................................................................197
Chapter 18 Collecting and Preparing the Sample for Analysis ..........................199
Collecting the Sample ......................................................................199
Preparing the Sample .......................................................................200
Grinding the Sample ........................................................................201
Cryogenic Grinding .....................................................................201
Sample Dissolution Methods ............................................................202
Choice of Reagents and Standards ...................................................204
Vessels, Containers, and Sample Preparation Equipment ................205