List of Contributors xvPreface xixAcknowledgment xxiiiSection 1 Fundamentals of Charged Aerosol Detection 11 Principles of Charged Aerosol Detection 3Paul Henri Gamache and Benjamin Eggart1.1 Summary 31.2 History and Introduction to CAD 41.2.1 Aerosol Basics 61.3 Charged Aerosol Detection Process 71.3.1 Spray Formation and Drying 71.3.1.1 Nebulization 71.3.1.2 Removal of Large Droplets 101.3.1.3 Evaporation 111.3.1.4 Volatility and Detector Response 121.3.2 Aerosol Charging 151.3.2.1 Unipolar Diffusion Charging 151.3.2.2 Summary of Aerosol Charging 181.3.3 Summary of CAD Process 181.4 CAD Response Model 201.4.1 Primary Droplet Size Distribution 211.4.2 Impactor 211.4.3 Drying and Residue Formation 221.4.3.1 Residue Particle Parameters 221.4.4 Charging of Residue Particles 221.4.5 Ion Removal 231.4.5.1 Attenuation of Particle Signal by Ion Trap 251.4.6 Signal Current 261.4.7 Signal from an Eluting Peak: Peak Shape 271.4.8 Peak Area Versus Injected Mass 281.4.9 Summary 281.5 Expected Performance 291.5.1 Response Curve: Shape and Dynamic Range 291.5.1.1 Signal Output—Power Function 321.5.1.2 Semivolatile Analytes 331.5.2 Sensitivity Limits 341.5.2.1 Eluent Impurities 351.5.3 Peak Shape 351.5.4 Mass Versus Concentration Sensitivity 351.5.5 Response Uniformity 371.5.5.1 Solvent Gradient Effects 371.5.5.2 Analyte Volatility and Salt Formation 381.5.5.3 Ionizable Solutes 381.5.5.4 Analyte Density 381.5.5.5 Dependence of Aerosol Measurement Technique on ResidueParticle Material 39References 412 Charged Aerosol Detection—Application Overview 47Ian Niel Acworth and Paul Henri Gamache2.1 Summary 472.2 Introduction 472.3 CAD History and Background 482.3.1 Liquid Flow Range 532.3.2 Temperature Control 532.3.3 Power Function Value 542.3.4 The Use of CAD with Different Chromatographic Techniques 542.4 CAD Publication Overview 552.5 CAD Publications by Analyte Classes 582.5.1 Carbohydrates 592.5.2 Drugs 602.5.3 Excipients 612.5.4 Lipids 622.5.5 Phytochemicals 64References 653 Practical Use of CAD—Achieving Optimal Performance 85Paul Henri Gamache, Ian Niel Acworth, Troy Handlovic, and Imad Haidar Ahmad3.1 Summary 853.2 Introduction 863.3 Factors Affecting Performance 873.3.1 Eluent Impurities 873.3.2 Mobile Phase Additives 893.3.3 Column Bleed 913.3.4 Mobile Phase Preparation 923.3.5 Chromatographic System 933.4 Evaporation Temperature 933.5 Calibration and Sensitivity Limits 943.5.1 Overview of CAD Response Curves 943.5.2 Approaches for Linearization of the CAD Signal in the Literature 963.5.3 Brief Theory of Power Transforms 983.5.4 Internal Power Function and User-Defined PFV 993.5.5 Optimizing the PFV 1003.5.6 Sensitivity Limits 1033.5.6.1 Recommended Practices for Calibration 1043.5.7 Summary of Calibration and Sensitivity Limits 104References 1044 Practical Realization of Response Uniformity and its Benefitsfor Global Quantification 109Frank Steiner, Katherine S. Lovejoy, and Paul Henri Gamache4.1 Summary 1094.2 Introduction 1104.3 Response Uniformity of EADs 1134.4 Factors Affecting the Response Uniformity of CAD 1144.4.1 Analyte Volatility 1154.4.2 Salt Formation with Ionizable Analytes 1164.4.3 Composition of Mobile Phase 1204.4.4 Influence of Solute Density 1214.5 Practical Strategies for Obtaining Uniform Response to Realize Global Quantification 1224.5.1 Uniform Response Using Isocratic Methods 1224.5.2 Uniform Response with Inverse Gradient Compensation 1234.5.3 Troubleshooting Inverse Gradient Compensation 1264.5.4 The Benefits of Linearizing Response to Universal Quantitation 1354.6 Conclusions 136References 137Section 2 Charged Aerosol Detection of Specific Analyte Classes 1435 Analysis of Lipids with Charged Aerosol Detection 145Paul Henri Gamache5.1 Summary 1455.2 Introduction 1465.3 Direct Comparisons of CAD and ELSD 1485.4 Case Studies 1505.4.1 Volatility and Evaporation Temperature (Te) 1505.4.2 Calibration and Power Function Value (PFV) 1535.4.3 Response Uniformity 1575.4.4 Analysis of Diverse Lipid Classes 1605.4.5 Chromatographic Variables Affecting CAD Performance 161References 1666 Analysis of Inorganic and Organic Ions with Charged Aerosol Detection 171Paul Henri Gamache6.1 Summary 1716.2 Introduction 1726.3 Practical Considerations 1736.3.1 Column Selectivity 1746.3.2 Column Bleed 1766.3.3 Mobile Phase 1786.3.4 Solvent Composition 1786.3.5 Additives 1796.3.6 Impurities, Contaminants, and Other Potential Issues 1816.3.7 Sensitivity and Linearity 1826.4 Applications 1846.4.1 Pharmaceutical and Biopharmaceutical Applications 1846.4.1.1 Counterions 1846.4.1.2 Raw Material Identification 1886.4.1.3 Impurity Ions in Pharmaceutical Products 1886.4.1.4 Parenteral Electrolyte-Amino Acid Solution 1896.4.1.5 Intracellular Ions 1896.4.1.6 Excipients Ions in Monoclonal Antibody (mAb) Formulations 1906.4.1.7 Excipient Ions in Antisense Oligonucleotide Drugs 1906.4.1.8 Ions in Drug-Loaded Liposomal Products 1916.4.1.9 Identification and Quantitation of Ionic Impurities in anInvestigational Drug 1926.4.2 Analysis of Ions in Dietary Supplements 1926.4.3 Bisphosphonate 1936.4.4 Ionic Liquids 195References 1967 Analysis of Carbohydrates with Charged Aerosol Detection 201Paul Henri Gamache7.1 Summary 2017.2 HPLC Analysis of Carbohydrates 2027.3 Practical Considerations with CAD 2047.3.1 Column Bleed 2057.3.2 Additives and Eluent pH 2097.3.3 Sensitivity, Linearity, and Calibration 2107.4 Representative Applications 2117.4.1 Therapeutic Glycoproteins and Vaccines 2137.4.2 Pharmaceuticals 2167.4.3 Food, Beverages, Plants and Traditional Herbs, and Medicines 220References 2248 Analysis of Pharmaceutical Excipients with Charged Aerosol Detection 229Ulrike Holzgrabe8.1 Summary 2298.2 Introduction 2298.3 Polyethylene glycols (Macrogols) and Derivatives 2318.4 Fatty Acids and Derivatives 2338.5 Carbohydrate Polymers and Derivatives 2368.6 Conclusions 238References 2389 Application of Charged Aerosol Detection in Traditional Herbal Medicines Analysis 243Baiping Ma, Ping Hu, Haizhen Liang, Yan Jin, and Guobin Shen9.1 Introduction 2439.2 Basic Ideas for Method Development of HPLC-CAD Analysis 2459.2.1 Factors Affecting CAD Sensitivity 2459.2.1.1 Effect of Mobile Phase Composition and Gradient on CAD Sensitivity 2459.2.1.2 Effect of Mobile Phase Flow Rate on CAD Sensitivity 2469.2.1.3 Effect of Evaporator Temperature on CAD Sensitivity 2469.2.1.4 Effect of Column Bleed on CAD Sensitivity 2469.2.2 Application of Fingerprint Chromatogram and Characteristic Chromatogram of TCM 2479.2.3 Quantitative and Semiquantitative Application in TCM 2509.2.3.1 Quantitative Analysis of Multi-components with a Single Marker 2509.2.3.2 Semiquantitative Method 2529.2.3.3 External Standard Method 2539.2.4 Combined Application of 2D-LC and CAD 2559.2.5 Fraction Collection Triggered by CAD 2589.3 Application of CAD in Quality Analysis of THMs 2599.3.1 Terpenoids/Saponins 2609.3.2 Carbohydrates 2639.3.3 Organic Acids 2659.3.4 Alkaloids 2699.3.5 Other Applications of CAD 2709.4 Conclusion 274References 274Section 3 Industrial Applications of Charged Aerosol Detection 28110 Analysis of Small Molecule Pharmaceuticals with Charged Aerosol Detection 283Ulrike Holzgrabe10.1 Summary 28310.2 Introduction 28410.3 Driving the Sensitivity of CAD 28510.4 Problem of the Nonlinear Response 28710.5 Advantage of a Universal Detector for Drug Quality Analysis 28910.6 Hyphenation of CAD and UV 29110.7 CAD in the International Pharmacopoeias 294References 29511 Analysis of Lipid-Based Formulations with Charged Aerosol Detection 299Claudia Seidl, Gabriel M. Leme, Charles R. Bupp, Andrei Blasko, and Imad A. Haidar Ahmad11.1 Introduction 29911.2 Chromatographic Considerations in the Analysis of LBFs 30311.2.1 Sample Preparation and Dilution Strategies 30311.2.2 Choosing the Chromatographic Mode for Analyzing LBFs 30411.2.3 Stationary-Phase Chemistry and Pore Size 30611.2.4 Mobile Phase Considerations 30711.3 Quantitation and Validation 31011.4 Applications of LC-CAD in LBFs Analysis 31911.4.1 Stability Assessment 31911.4.2 Formulation Development 321References 32212 Application of Charged Aerosol Detection in Polysorbate Analysis 325Jessica Lin, Juan Bian, Frank Hrovat, and Kelly Zhang12.1 Introduction 32512.1.1 Overview of Polysorbates in Biopharmaceuticals 32512.1.2 Challenges in Polysorbate Analysis 32612.2 Analytical Technology of Polysorbates 32612.2.1 Separation of Polysorbates 32612.2.2 Detection of Polysorbates 32812.3 Applications of CAD in Polysorbate Analysis 33012.3.1 Characterization of Polysorbate Components 33012.3.2 Polysorbate Stability in Biopharmaceutical Formulations 33112.3.3 Quantification of Polysorbates 33712.4 Emerging Trends and Future Directions 33812.4.1 Advancements in CAD Technology 33812.4.2 Automated and High-Throughput Applications 33912.4.3 Multi-Detector Systems 33912.5 Conclusion 340References 34013 Use of Orthogonal Detectors in Comprehensive Analyses: A Focus on Safety Assessment of Pharmaceuticals, Including Botanicals 345Katherine Lovejoy and Frank Steiner13.1 Summary 34513.2 Introduction to Comprehensive Analysis 34613.2.1 Advantages of Untargeted Analysis by CAD 34613.2.2 LC× LC with CAD 34713.3 Principles of the Implementation of Orthogonal Detectors 34813.3.1 Sensitivity in Multidetector Setups 34813.3.2 Quantification and Uniform Response of CAD 34813.3.3 Control of the Split to Destructive Detectors 35113.3.4 Eluent Compatibility, System Back Pressure and System Dead Volume 35413.3.5 Strategies for Data Analysis 35513.4 Application Examples for Comprehensive Analysis 35613.4.1 Comprehensive Analysis by CAD: Safety Assessment of Botanicals 35613.4.2 Comprehensive Analysis by CAD: Extractables and Leachables 36013.5 Conclusions 363References 36414 CAD in Drug Discovery 369Wesley W. Barnhart, Troy T. Handlovic, Brian A. Lanman, David Bauer, and Imad A. Haidar Ahmad14.1 Summary 36914.2 Introduction 37014.3 Streamlining Drug Discovery 37014.4 Chromatography-BasedWorkflows in Drug Discovery 37214.5 Use and Benefits of CAD in Discovery 37414.6 Microgram High-Throughput Purification PlatformWorkflow 37614.6.1 Purification 37614.6.2 Drying and Reformatting 37814.6.3 Post-QC Analysis 37914.6.4 Data Analysis 38014.6.5 CAD Optimization, Calibration, and Results 38014.7 Conclusion 383References 38315 Applications of Charged Aerosol Detection for Characterization of Industrial Polymers 389Paul Cools and Ton Brooijmans15.1 Introduction 38915.2 Liquid Chromatography of Polymers 39015.3 Solvents 39315.4 Quantitative Detection of Polymer Molecules 39515.4.1 Ultraviolet Detection 39515.4.2 Differential Refractive Index Detection 39515.4.3 Evaporative Detection 39615.4.4 Charged Aerosol Detection 39615.4.5 Molar Mass-Dependent Detection 39715.4.6 Mass Spectrometry 39715.5 Size Exclusion Chromatography and Charged Aerosol Detection 39815.6 Gradient Polymer Elution Chromatography and CAD 40515.7 Liquid Chromatography Combined with UV, CAD, and MS Detection 40915.7.1 LC-ESI-TOF-MS System at DSM Coating Resins 41015.8 Typical Examples of Industrial Applications Using LC-MS-CAD 41115.8.1 Raw Material Analysis 41215.8.2 Intermediates 41315.8.3 End Products 41415.9 Epilogue 416Acknowledgments 416References 416Index 421
Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques - Ian N. Acworth - Inbunden | Bokus
