Description
Book SynopsisThis is the first book dedicated to charged aerosol detection for HPLC and related techniques. It provides detailed insight into the actual and potential applications of charged aerosol detection across a wide range of industries, thereby enabling improved detection of a range of analytes.
Table of ContentsList of Contributors xvii
Preface xxi
Acknowledgment xxv
Section 1 Fundamentals of Charged Aerosol Detection 1
1 Principles of Charged Aerosol Detection 3
Paul H. Gamache and Stanley L. Kaufman
1.1 Summary 3
1.2 History and Introduction to the Technology 4
1.3 Charged Aerosol Detection Process 9
1.3.1 Nebulization 9
1.3.2 Aerosol Conditioning 13
1.3.2.1 Solvent Load Reduction 13
1.3.2.2 Secondary Processes 13
1.3.2.3 Summary: Aerosol Transport 16
1.3.3 Evaporation 16
1.3.3.1 Aerosol Evaporation Process 17
1.3.3.2 Evaporation Rate (Re) 17
1.3.3.3 Dried Particle Size 19
1.3.3.4 Volatility and Detector Response 20
1.3.3.5 Particle Size Dependency 20
1.3.3.6 Ionizable Solutes 21
1.3.3.7 Background Solutes: Impurities 22
1.3.3.8 Summary 24
1.3.4 Aerosol Charging 24
1.3.4.1 Mechanisms 24
1.3.4.2 Diffusion Charging Overview 25
1.3.4.3 Unipolar Diffusion Charging Theory 26
1.3.4.4 CAD “Corona Jet” Charger Design 27
1.3.4.5 Corona Ion Jet and Aerosol Particle Jet 28
1.3.5 Summary of Aerosol Charging 29
1.3.6 Summary of CAD Process 29
1.4 CAD Response Model 31
1.4.1 Primary Droplet Size Distribution 32
1.4.2 Impactor 32
1.4.3 Drying and Residue Formation 33
1.4.3.1 Residue Particle Parameters 33
1.4.4 Charging of Residue Particles 33
1.4.5 Ion Removal 34
1.4.5.1 Attenuation of Particle Signal by Ion Trap 36
1.4.6 Signal Current 37
1.4.7 Signal from an Eluting Peak: Peak Shape 38
1.4.8 Peak Area Versus Injected Mass 39
1.4.9 Summary 39
1.5 Performance Characteristics 40
1.5.1 Response Curve: Shape and Dynamic Range 40
1.5.1.1 Semivolatile Analytes 44
1.5.1.2 Calibration 45
1.5.2 Peak Shape 48
1.5.3 Mass Versus Concentration Sensitivity 49
1.5.4 Sensitivity Limits 51
1.5.5 Response Uniformity 52
1.5.5.1 Solvent Gradient Effects 53
1.5.5.2 Analyte Volatility and Salt Formation 53
1.5.5.3 Analyte Density 54
1.5.5.4 Dependence of Aerosol Measurement Technique on Residue Particle Material 54
1.5.6 CAD Versus Formation of Gaseous Ions for MS 56
1.5.6.1 Pneumatically Assisted ESI 57
1.5.6.2 APCI 57
1.5.6.3 Main Differences between CAD and MS 58
References 59
2 Charged Aerosol Detection: A Literature Review 67
Ian N. Acworth and William Kopaciewicz
2.1 Introduction 67
2.2 CAD History and Background 74
2.3 Application Areas 79
2.3.1 Carbohydrates 79
2.3.2 Lipids 79
2.3.3 Natural Products 86
2.3.4 Pharmaceutical and Biopharmaceutical Analysis 86
2.3.5 Other Application Areas 131
2.4 Conclusions 131
Acknowledgements 131
References 141
3 Practical Use of CAD: Achieving Optimal Performance 163
Bruce Bailey, Marc Plante, David Thomas, Chris Crafts, and Paul H. Gamache
3.1 Summary 163
3.2 Introduction 164
3.2.1 First‐ and Second‐Generation Instrument Designs 165
3.2.2 Liquid Flow Range 165
3.2.3 Excess Liquid Removal 167
3.2.4 Temperature Control 167
3.2.5 Aerosol Creation and Transport 167
3.3 Factors Influencing CAD Performance 168
3.3.1 Analyte Properties 168
3.3.1.1 Formation of Aerosol Residue Particles 168
3.3.1.2 Inherent Response of Downstream Aerosol Detector 169
3.3.1.3 Summary of Analyte Properties 169
3.3.2 Eluent Properties and Composition 169
3.3.2.1 Mass Transport 169
3.3.2.2 Eluent Purity 170
3.3.2.3 Mobile Phase Additives 171
3.3.2.4 Additional Sources of Eluent Impurities 173
3.3.2.5 Column Bleed 174
3.3.2.6 Basic Eluents 174
3.3.2.7 System Components and Laboratory Equipment 175
3.3.2.8 Summary 176
3.4 System Configurations 177
3.4.1 Microscale LC 177
3.4.2 Post‐column Addition 177
3.4.3 Multi‐detector Configurations 178
3.5 Method Transfer 180
3.6 Calibration and Sensitivity Limits 182
3.6.1 Power Function 185
3.6.2 Summary of Calibration and Sensitivity Limits 186
References 186
4 Aerosol‐Based Detectors in Liquid Chromatography: Approaches Toward Universal Detection and to Global Analysis 191
Joseph P. Hutchinson, Greg W. Dicinoski, and Paul R. Haddad
4.1 Summary 191
4.2 Introduction 192
4.3 Universal Detection Methods 194
4.4 Factors Affecting the Response in Charged Aerosol Detection 198
4.5 Gradient Compensation 204
4.6 Response Models 205
4.7 Green Chemistry 206
4.8 Temperature Gradient Separations 209
4.9 Supercritical CO 2 Separations 210
4.10 Capillary Separations 211
4.11 Global Analysis and Multidimensional Separations 212
4.12 Conclusions 215
References 216
Section 2 Charged Aerosol Detection of Specific Analyte Classes 221
5 Lipid Analysis with the Corona CAD 223
Danielle Libong, Sylvie Héron, Alain Tchapla, and Pierre Chaminade
5.1 Introduction 223
5.2 Principles of Chromatographic Separation of Lipids 227
5.2.1 Theory of Retention Mechanism in Reversed‐Phase Liquid Chromatography 227
5.2.2 Optimizing Selectivity 231
5.2.3 Note on Using pH Modifiers for Selectivity Optimization 235
5.3 Application: Strategy of Lipid Separation 235
5.3.1 Separation of Individual Lipid Classes 236
5.3.2 Separation of Subclasses of Lipids 240
5.3.2.1 Size Exclusion Chromatography 240
5.3.2.2 Argentation Chromatography 241
5.3.3 Separation of Congeners Belonging to Specific Classes of Lipids 242
5.3.4 Behavior of Lipid Separation in Reversed‐Phase Chromatography 246
5.3.5 Behavior of Lipid Separation in Reversed‐Phase Sub‐ and Supercritical Fluid Chromatography 250
5.3.6 Multimodal Chromatographic Systems 252
5.3.7 Identification of the Molecular Species 252
5.3.7.1 Methodology for Identification of Congeners 256
5.4 Literature Review: Early Use of Corona CAD in Lipid Analysis 257
5.4.1 Biosciences 257
5.4.2 Food Chemistry 258
5.4.3 Pharmaceutical Sciences 260
5.4.3.1 Emulsions 260
5.4.3.2 Liposomes 261
5.4.3.3 Surfactants 262
5.4.3.4 Contrast Agents 263
5.4.3.5 Determination of Degradation Product and Impurities 263
5.5 Calibration Strategies 264
5.5.1 Calibration Strategies in Quantitative Analysis of Lipids 264
5.5.2 Classical Calibration (External Calibration, Normalization) 266
5.5.3 Calibration in Absence of Standards 268
References 272
6 Inorganic and Organic Ions 289
Xiaodong Liu, Christopher A. Pohl, and Ke Zhang
6.1 Introduction 289
6.2 Technical Considerations 291
6.2.1 Instrumentation Platform 291
6.2.2 Separation Column 292
6.2.3 Mobile Phase 295
6.2.4 CAD Parameter Setting 297
6.2.5 Sensitivity 297
6.2.6 Calibration Curve, Dynamic Range, Accuracy, and Precision 298
6.3 Applications 300
6.3.1 Pharmaceutical Counterions and Salts 301
6.3.2 Bisphosphonate 303
6.3.3 Phosphorylated Carbohydrates 304
6.3.4 Ionic Liquids 304
6.3.5 Pesticides 305
6.3.6 Other Applications 305
6.4 Concluding Remarks 306
References 306
7 Determination of Carbohydrates Using Liquid Chromatography with Charged Aerosol Detection 311
Jeffrey S. Rohrer and Shinichi Kitamura
7.1 Summary 311
7.2 Liquid Chromatography of Carbohydrates 312
7.3 Charged Aerosol Detection 314
7.4 Why LC‐CAD for Carbohydrate Analysis? 315
7.5 Early Applications of CAD to Carbohydrate Analysis 316
7.6 Additional Applications of CAD to Carbohydrate Analysis 317
References 322
8 Polymers and Surfactants 327
Dawen Kou, Gerald Manius, Hung Tian, and Hitesh P. Chokshi
8.1 Summary 327
8.2 Introduction 328
8.3 Polymer Analysis 328
8.4 Polyethylene Glycol 329
8.4.1 PEG Reagents 330
8.4.2 Low Molecular Weight PEGs 333
8.4.3 PEGylated Molecules 335
8.5 Surfactants 336
References 339
9 Application of Charged Aerosol Detection in Traditional Herbal Medicines 341
Lijuan Liang, Yong Jiang, and Pengfei Tu
9.1 Summary 341
9.2 Introduction 342
9.3 Factors that Affect the Sensitivity of CAD 343
9.3.1 Mobile Phase Composition 343
9.3.2 Effects of Nitrogen Gas Purity on the Sensitivity of CAD 344
9.3.3 The Effect of Mobile Phase Modifiers 344
9.3.4 Comparison of Flow Rate Effect on the Sensitivity of CAD 345
9.4 Application of CAD in Quality Analysis of Traditional Herbal Medicines 345
9.4.1 Determination of Saponins in Radix et Rhizoma Notoginseng by CAD Coupled with HPLC 345
9.4.2 Determination of Ginsenosides by LC‐CAD 346
9.4.3 Other Applications of CAD 349
9.5 Conclusion 353
References 353
Section 3 Industrial Applications of Charged Aerosol Detection 355
10 Charged Aerosol Detection in Pharmaceutical Analysis: An Overview 357
Michael Swartz, Mark Emanuele, and Amber Awad
10.1 Summary 357
10.2 Introduction 358
10.3 Analytical Method Development 359
10.4 Analytical Method Validation 361
10.5 CAD in Analytical Method Transfer 363
10.6 CAD in Formulation Development and Ion Analysis 364
10.7 Carbohydrate Analysis by CAD 368
10.8 CAD in Stability Analyses 371
10.9 Conclusion 373
References 374
11 Impurity Control in Topiramate with High Performance Liquid Chromatography: Validation and Comparison of the Performance of Evaporative Light Scattering Detection and Charged Aerosol Detection 379
David Ilko, Robert C. Neugebauer, Sophie Brossard, Stefan Almeling, Michael Türck, and Ulrike Holzgrabe
11.1 Summary 379
11.2 Introduction 380
11.3 Material and Methods 382
11.3.1 Reagents and Material 382
11.3.2 HPLC–ELSD/CAD 382
11.3.3 TLC and HPTLC Limit Test for Impurity A 383
11.4 Results and Discussion 383
11.4.1 Method Validation: Impurity Control 383
11.4.2 Method Validation: Assay 388
11.4.3 TLC and HPTLC Limit Test for Impurity A 390
11.5 Conclusion 390
Acknowledgment 390
References 391
12 Applying Charged Aerosol Detection to Aminoglycosides: Development and Validation of an RP‐HPLC Method for Gentamicin and Netilmicin 393
Arul Joseph and Abu Rustum
12.1 Introduction 393
12.1.1 Background 394
12.2 Development and Validation of an RP‐HPLC Method for Gentamicin Using Charged Aerosol Detection 395
12.2.1 Method Development 395
12.2.1.1 Selection of Detector 395
12.2.1.2 Related Substances 395
12.2.1.3 Mobile Phase Composition and Column Selection 398
12.2.1.4 Sample Preparation 400
12.2.2 Method Validation 402
12.2.2.1 Experimental 402
12.2.2.2 Specificity 403
12.2.2.3 Linearity 403
12.2.2.4 Accuracy 404
12.2.2.5 Limit of Detection and Limit of Quantitation 405
12.2.2.6 Reproducibility and Precision 406
12.2.2.7 Robustness 406
12.2.2.8 Alternate Column Validation 406
12.2.2.9 Calculation 407
12.2.2.10 Chromatographic Conditions of the Final Method 409
12.2.3 Discussion 409
12.3 Application of Strategy to Netilmicin Sulfate 410
12.3.1 Method Development 410
12.3.1.1 Sample Preparation 414
12.3.2 Method Validation 415
12.3.2.1 Specificity 415
12.3.2.2 Linearity 415
12.3.2.3 Limit of Detection and Limit of Quantitation 417
12.3.2.4 Robustness 417
12.3.2.5 Calculation 418
12.3.2.6 Chromatographic Conditions of the Final Method 418
12.3.3 Discussion 418
12.4 Conclusion 420
Acknowledgments 420
References 420
13 Determination of Quaternary Ammonium Muscle Relaxants with Their Impurities in Pharmaceutical Preparations by LC‐CAD 425
Agata Blazewicz, Magdalena Poplawska, Malgorzata Warowna‐Grzeskiewicz, Katarzyna Sarna, and Zbigniew Fijalek
13.1 Summary 425
13.2 Introduction 426
13.3 Experimental 429
13.3.1 Equipment and Conditions 429
13.3.2 Material Studied 430
13.3.3 Standard Solutions 431
13.4 Results and Discussion 431
13.4.1 Selection of Chromatographic Conditions 431
13.4.1.1 LC‐CAD Method for Atracurium, Cisatracurium, and Mivacurium and Their Impurities 431
13.4.1.2 LC‐CAD Method for Pancuronium and Its Impurities 432
13.4.2 Identification of Analytes 434
13.4.3 Validation of the Methods 434
13.4.3.1 Linearity 436
13.4.3.2 Detection and Quantitation Limits 438
13.4.3.3 Precision and Accuracy 441
13.4.3.4 Range 442
13.4.4 Determination of Active Substances and Impurities in Pharmaceutical Preparations 443
13.4.5 Stability 443
13.5 Conclusion 445
Acknowledgments 445
References 446
14 Charged Aerosol Detection of Scale Inhibiting Polymers in Oilfield Chemistry Applications 449
Alan K. Thompson
14.1 Summary 449
14.2 Background to Scale Inhibition in Oilfields 450
14.2.1 General Background 450
14.2.2 Squeeze Programs 452
14.2.3 Polymeric Inhibitors 454
14.3 Historical Methods of Analysis 455
14.4 Charged Aerosol Detection for Polymeric Scale Inhibitors 459
14.4.1 Theoretical Application of CAD 459
14.4.2 Practical Application of CAD 460
14.4.3 Typical Validation of Methodology 461
14.4.3.1 Linearity of Detection 462
14.4.3.2 Precision of Injection 463
14.4.3.3 Assay Accuracy and Precision 464
14.4.3.4 Assay Ruggedness 464
14.4.3.5 Assay Ruggedness 2: Inter‐instrument Variability 465
14.4.3.6 Limit of Detection and Limit of Quantification 466
14.4.3.7 Analysis of Routine Oilfield Brine Samples for Polymeric Scale Inhibitor Using HPLC‐CAD 466
14.4.4 Limits of Methodology 467
14.5 Conclusions and Further Work 468
References 469
15 Applications of Charged Aerosol Detection for Characterization of Industrial Polymers 471
Paul Cools and Ton Brooijmans
15.1 Introduction 471
15.2 Liquid Chromatography of Polymers 472
15.3 Solvents 475
15.4 Quantitative Detection of Polymer Molecules 476
15.4.1 Ultraviolet Detection 476
15.4.2 Differential Refractive Index Detection 476
15.4.3 Evaporative Detection 477
15.4.4 Charged Aerosol Detection 477
15.4.5 Molar Mass Dependent Detection 478
15.4.6 Mass Spectrometry 478
15.5 Size Exclusion Chromatography and Charged Aerosol Detection 479
15.6 Gradient Polymer Elution Chromatography and CAD 486
15.7 Liquid Chromatography Combined with UV, CAD, and MS Detection 490
15.7.1 LC‐ESI‐TOF MS System at DSM Coating Resins 491
15.8 Typical Examples of Industrial Applications Using LC‐MS‐CAD 492
15.8.1 Raw Material Analysis 493
15.8.2 Intermediates 494
15.8.3 End Products 495
15.9 Epilogue 497
Acknowledgments 497
References 497
Index 501
