{"product_id":"hplc-for-pharmaceutical-scientists-hardback-9780471681625","title":"HPLC for Pharmaceutical Scientists (Hardback) 9780471681625","description":"\u003cfont face=\"Georgia\"\u003e\r\n\u003cp\u003e\u003cfont size=\"6\"\u003eHPLC for Pharmaceutical Scientists\u003c\/font\u003e\u003cbr\u003e\r\n\r\n\r\n\r\n\r\n\r\n\u003c\/p\u003e\n\u003cp\u003e\u003cfont size=\"4\"\u003eYuri V. Kazakevich (Author), Rosario LoBrutto (Author)\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e9780471681625, Wiley\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003eHardback, published 22 January 2007\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e1136 pages, Charts: 25 B\u0026amp;W, 0 Color; Photos: 9 B\u0026amp;W, 0 Color; Drawings: 95 B\u0026amp;W, 5 Color; Screen captures: 9 B\u0026amp;W, 0 Color; Tables: 115 B\u0026amp;W, 0 Color; Graphs: 309 B\u0026amp;W, 0 Color\u003cbr\u003e24.1 x 16.3 x 5.8 cm, 1.724 kg\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\r\n\u003cp align=\"justify\"\u003e\u003cem\u003e\u003cfont size=\"3\"\u003e\"Without question LC\/MS is the most dominant application of mass spectrometry in the pharmaceutical industry ... That being said, the editors should be commended for how well they took on such a comprehensive subject and worked with several recognized contributors to make a text that is both manageable and highly informative.\" (J Am Soc Mass Spectrom, 2007)  \u003cp\u003e \"...extremely useful and quite extensive in its coverage of the subject...\" (\u003ci\u003eJournal of the American Chemical Society\u003c\/i\u003e, July 18, 2007)\u003c\/p\u003e\u003c\/font\u003e\u003c\/em\u003e\u003c\/p\u003e\r\n\r\n\u003cp align=\"justify\"\u003e\u003cstrong\u003e\u003cfont size=\"3\"\u003e\u003ci\u003eHPLC for Pharmaceutical Scientists\u003c\/i\u003e is an excellent book for both novice and experienced pharmaceutical chemists who regularly use HPLC as an analytical tool to solve challenging problems in the pharmaceutical industry. It provides a unified approach to HPLC with an equal and balanced treatment of the theory and practice of HPLC in the pharmaceutical industry.  \u003cp\u003eIn-depth discussion of retention processes, modern HPLC separation theory, properties of stationary phases and columns are well blended with the practical aspects of fast and effective method development and method validation. Practical and pragmatic approaches and actual examples of effective development of selective and rugged HPLC methods from a physico-chemical point of view are provided.\u003c\/p\u003e \u003cp\u003eThis book elucidates the role of HPLC throughout the entire drug development process from drug candidate inception to marketed drug product and gives detailed specifics of HPLC application in each stage of drug development.\u003c\/p\u003e \u003cp\u003eThe latest advancements and trends in hyphenated and specialized HPLC techniques (LC-MS, LC-NMR, Preparative HPLC, High temperature HPLC, high pressure liquid chromatography) are also discussed.\u003c\/p\u003e\u003c\/font\u003e\u003c\/strong\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e\u003cp\u003ePreface xxi\u003c\/p\u003e \u003cp\u003eContributors xxv\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart I Hplc Theory and Practice 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Introduction 3\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYuri Kazakevich and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Chromatography in the Pharmaceutical World, 3\u003c\/p\u003e \u003cp\u003e1.2 Chromatographic Process, 4\u003c\/p\u003e \u003cp\u003e1.3 Classification, 4\u003c\/p\u003e \u003cp\u003e1.4 History of Discovery and Early Development (1903–1933), 6\u003c\/p\u003e \u003cp\u003e1.5 General Separation Process, 8\u003c\/p\u003e \u003cp\u003e1.5.1 Modern HPLC Column, 9\u003c\/p\u003e \u003cp\u003e1.5.2 HPLC System, 9\u003c\/p\u003e \u003cp\u003e1.6 Types of HPLC, 10\u003c\/p\u003e \u003cp\u003e1.6.1 Normal-Phase Chromatography (NP HPLC), 10\u003c\/p\u003e \u003cp\u003e1.6.2 Reversed-Phase HPLC (RP HPLC or RPLC), 11\u003c\/p\u003e \u003cp\u003e1.6.3 Ion-Exchange Chromatography (IEX), 13\u003c\/p\u003e \u003cp\u003e1.6.4 Size-Exclusion Chromatography (SEC), 14\u003c\/p\u003e \u003cp\u003e1.7 HPLC Descriptors (Vr, k, N, etc.), 15\u003c\/p\u003e \u003cp\u003e1.7.1 Retention Volume, 15\u003c\/p\u003e \u003cp\u003e1.7.2 Void Volume, 16\u003c\/p\u003e \u003cp\u003e1.7.3 Retention Factor, 17\u003c\/p\u003e \u003cp\u003e1.7.4 Selectivity, 18\u003c\/p\u003e \u003cp\u003e1.7.5 Efficiency, 19\u003c\/p\u003e \u003cp\u003e1.7.6 Resolution, 22\u003c\/p\u003e \u003cp\u003eReferences, 23\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 HPLC Theory 25\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYuri Kazakevich\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction, 25\u003c\/p\u003e \u003cp\u003e2.2 Basic Chromatographic Descriptors, 26\u003c\/p\u003e \u003cp\u003e2.3 Efficiency, 27\u003c\/p\u003e \u003cp\u003e2.4 Resolution, 32\u003c\/p\u003e \u003cp\u003e2.5 HPLC Retention, 34\u003c\/p\u003e \u003cp\u003e2.6 Retention Mechanism, 35\u003c\/p\u003e \u003cp\u003e2.7 General Column Mass Balance, 37\u003c\/p\u003e \u003cp\u003e2.8 Partitioning Model, 39\u003c\/p\u003e \u003cp\u003e2.9 Adsorption Model, 40\u003c\/p\u003e \u003cp\u003e2.10 Total and Excess Adsorption, 41\u003c\/p\u003e \u003cp\u003e2.11 Mass Balance in Adsorption Model, 42\u003c\/p\u003e \u003cp\u003e2.12 Adsorption of the Eluent Components, 43\u003c\/p\u003e \u003cp\u003e2.13 Void Volume Considerations, 47\u003c\/p\u003e \u003cp\u003e2.14 Thermodynamic Relationships, 49\u003c\/p\u003e \u003cp\u003e2.14.1 Effect of the Eluent Composition, 53\u003c\/p\u003e \u003cp\u003e2.15 Adsorption-Partitioning Retention Mechanism, 54\u003c\/p\u003e \u003cp\u003e2.16 Secondary Equilibria, 57\u003c\/p\u003e \u003cp\u003e2.16.1 Inclusion of Secondary Equilibria in the Mass Balance, 58\u003c\/p\u003e \u003cp\u003e2.16.2 Salt Effect, 62\u003c\/p\u003e \u003cp\u003e2.17 Gradient Elution Principles, 67\u003c\/p\u003e \u003cp\u003e2.18 Types of Analyte Interactions with the Stationary Phase, 69\u003c\/p\u003e \u003cp\u003e2.19 Conclusion, 70\u003c\/p\u003e \u003cp\u003eReferences, 71\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Stationary Phases 75\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYuri Kazakevich and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction, 75\u003c\/p\u003e \u003cp\u003e3.2 Type of Packing Material (Porous, Nonporous, Monolithic), 77\u003c\/p\u003e \u003cp\u003e3.3 Base Material (Silica, Zirconia, Alumina, Polymers), 77\u003c\/p\u003e \u003cp\u003e3.4 Geometry, 80\u003c\/p\u003e \u003cp\u003e3.4.1 Shape (Spherical\/Irregular), 80\u003c\/p\u003e \u003cp\u003e3.4.2 Particle Size Distribution, 80\u003c\/p\u003e \u003cp\u003e3.4.3 Surface Area, 81\u003c\/p\u003e \u003cp\u003e3.4.4 Pore Volume, 82\u003c\/p\u003e \u003cp\u003e3.4.5 Surface Geometry, 84\u003c\/p\u003e \u003cp\u003e3.5 Adsorbent Surface Chemistry, 85\u003c\/p\u003e \u003cp\u003e3.5.1 Surface Chemistry of the Base Material, 85\u003c\/p\u003e \u003cp\u003e3.5.2 Silica, 86\u003c\/p\u003e \u003cp\u003e3.5.3 Silica Hybrid, 88\u003c\/p\u003e \u003cp\u003e3.5.4 Polymeric Packings, 89\u003c\/p\u003e \u003cp\u003e3.5.5 Zirconia (Metal Oxides), 90\u003c\/p\u003e \u003cp\u003e3.5.6 Porous Carbon (or Carbon-Coated Phases), 90\u003c\/p\u003e \u003cp\u003e3.6 Surface of Chemically Modified Material, 91\u003c\/p\u003e \u003cp\u003e3.6.1 Limits of Surface Modification, 93\u003c\/p\u003e \u003cp\u003e3.6.2 Chemical Modification, 93\u003c\/p\u003e \u003cp\u003e3.6.3 Types of Bonded Phases, 101\u003c\/p\u003e \u003cp\u003e3.6.4 Structure of the Bonded Layer, 103\u003c\/p\u003e \u003cp\u003e3.6.5 Density of Bonded Ligands, 105\u003c\/p\u003e \u003cp\u003e3.6.6 Residual Silanoles, 110\u003c\/p\u003e \u003cp\u003e3.6.7 Surface Area of Modified Adsorbent, 110\u003c\/p\u003e \u003cp\u003e3.7 Polymer-Based Adsorbents, 113\u003c\/p\u003e \u003cp\u003e3.8 Stationary Phases for Chiral Separations, 115\u003c\/p\u003e \u003cp\u003e3.8.1 Polysaccharide-Coated Phases, 115\u003c\/p\u003e \u003cp\u003e3.8.2 Pirkle-Type Phases, 116\u003c\/p\u003e \u003cp\u003e3.8.3 Protein Phases, 116\u003c\/p\u003e \u003cp\u003e3.8.4 Molecular Imprinted Polymers for Chiral Separations, 117\u003c\/p\u003e \u003cp\u003e3.9 Columns, 118\u003c\/p\u003e \u003cp\u003e3.9.1 Capillary\/Monolithic\/Packed Columns, 118\u003c\/p\u003e \u003cp\u003e3.9.2 Column Cleaning, 126\u003c\/p\u003e \u003cp\u003e3.9.3 Column Void Volume, 128\u003c\/p\u003e \u003cp\u003e3.9.4 Mass of Adsorbent in the Column, 130\u003c\/p\u003e \u003cp\u003eReferences, 132\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Reversed-Phase HPLC 139\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRosario LoBrutto and Yuri Kazakevich\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction, 139\u003c\/p\u003e \u003cp\u003e4.2 Retention in Reversed-Phase HPLC, 140\u003c\/p\u003e \u003cp\u003e4.3 Stationary Phases for RPLC, 142\u003c\/p\u003e \u003cp\u003e4.4 Mobile Phases for RPLC, 145\u003c\/p\u003e \u003cp\u003e4.4.1 Eluent Composition and Solvent Strength of the Mobile Phase, 146\u003c\/p\u003e \u003cp\u003e4.4.2 Type of Organic Modifier, 151\u003c\/p\u003e \u003cp\u003e4.4.3 Selectivity as a Function of Type and Concentration of Organic Composition, 153\u003c\/p\u003e \u003cp\u003e4.5 pH Effect on HPLC Separations, 158\u003c\/p\u003e \u003cp\u003e4.5.1 Mobile-Phase pH. Practical Considerations, 158\u003c\/p\u003e \u003cp\u003e4.5.2 Analyte Ionization (Acids, Bases, Zwitterions), 160\u003c\/p\u003e \u003cp\u003e4.5.3 pK a and pK b Relationship, 161\u003c\/p\u003e \u003cp\u003e4.5.4 Retention of Ionizible Analytes in Reversed-Phase Hplc, 161\u003c\/p\u003e \u003cp\u003e4.5.5 Case Studies: Effects of pH on Ionizable Analyte Retention, 166\u003c\/p\u003e \u003cp\u003e4.5.6 Mobile-Phase pH, 171\u003c\/p\u003e \u003cp\u003e4.5.7 Analyte Dissociation Constants, 179\u003c\/p\u003e \u003cp\u003e4.5.8 Determination of Chromatographic pK a , 180\u003c\/p\u003e \u003cp\u003e4.6 Effect of Organic Eluent Composition on Analyte Ionization, 182\u003c\/p\u003e \u003cp\u003e4.6.1 Effect of Organic Modifier on Basic Analyte pK a Shift, 182\u003c\/p\u003e \u003cp\u003e4.6.2 Effect of Organic Modifier on Acidic Analyte pK a Shift, 186\u003c\/p\u003e \u003cp\u003e4.7 Synergistic Effect of pH, Organic Eluent, and Temperature on Ionizable Analyte Retention and Selectivity, 189\u003c\/p\u003e \u003cp\u003e4.8 Examples of Applying pH Shift and Analyte pK a Shift Rules, 191\u003c\/p\u003e \u003cp\u003e4.9 Effect of Temperature on Analyte Ionization, 195\u003c\/p\u003e \u003cp\u003e4.10 Ion-Interaction Chromatography, 197\u003c\/p\u003e \u003cp\u003e4.10.1 Introduction, 197\u003c\/p\u003e \u003cp\u003e4.10.2 Double Layer Theory, 198\u003c\/p\u003e \u003cp\u003e4.10.3 Ion Pairs, 200\u003c\/p\u003e \u003cp\u003e4.10.4 Chaotropic Effect, 206\u003c\/p\u003e \u003cp\u003e4.11 Concluding Remarks, 227\u003c\/p\u003e \u003cp\u003eReferences, 228\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Normal-Phase HPLC 241\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYong Liu and Anant Vailaya\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction, 241\u003c\/p\u003e \u003cp\u003e5.2 Theory of Retention in Normal-Phase Chromatography, 241\u003c\/p\u003e \u003cp\u003e5.3 Effect of Mobile Phase on Retention, 245\u003c\/p\u003e \u003cp\u003e5.4 Selectivity, 248\u003c\/p\u003e \u003cp\u003e5.4.1 Effect of Analyte Structure, 248\u003c\/p\u003e \u003cp\u003e5.4.2 Types of Stationary Phases, 249\u003c\/p\u003e \u003cp\u003e5.5 Applications, 251\u003c\/p\u003e \u003cp\u003e5.5.1 Analytes Prone to Hydrolysis, 251\u003c\/p\u003e \u003cp\u003e5.5.2 Extremely Hydrophobic Compounds, 252\u003c\/p\u003e \u003cp\u003e5.5.3 Separation of Isomers, 253\u003c\/p\u003e \u003cp\u003e5.5.4 Carbohydrates, 256\u003c\/p\u003e \u003cp\u003e5.5.5 Separation of Saturated\/Unsaturated Compounds, 257\u003c\/p\u003e \u003cp\u003e5.6 Conclusions, 257\u003c\/p\u003e \u003cp\u003eReferences, 257\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Size-Exclusion Chromatography 263\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYuri Kazakevich and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Separation of the Analyte Molecules by Their Size, 263\u003c\/p\u003e \u003cp\u003e6.2 Molecular Size and Molecular Weight, 266\u003c\/p\u003e \u003cp\u003e6.3 Separation Mechanism, 267\u003c\/p\u003e \u003cp\u003e6.4 Calibration, 268\u003c\/p\u003e \u003cp\u003e6.5 Columns, 271\u003c\/p\u003e \u003cp\u003e6.6 Molecular Weight Distribution, 273\u003c\/p\u003e \u003cp\u003e6.7 Effect of Eluent, 274\u003c\/p\u003e \u003cp\u003e6.8 Effect of Temperature, 274\u003c\/p\u003e \u003cp\u003e6.9 Detectors, 275\u003c\/p\u003e \u003cp\u003e6.10 Solving Mass Balance Issues, 275\u003c\/p\u003e \u003cp\u003e6.11 Aqueous SEC Applications, 276\u003c\/p\u003e \u003cp\u003eReferences, 278\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 LC\/MS: Theory, Instrumentation, and Applications to Small Molecules 281\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eGuodong Chen, Li-Kang Zhang, and Birendra N. Pramanik\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction, 281\u003c\/p\u003e \u003cp\u003e7.2 Ionization Methods and LC\/MS Interfaces, 282\u003c\/p\u003e \u003cp\u003e7.2.1 Ionization Methods, 282\u003c\/p\u003e \u003cp\u003e7.2.2 Historical View of Interfaces, 286\u003c\/p\u003e \u003cp\u003e7.2.3 Common Interfaces, 288\u003c\/p\u003e \u003cp\u003e7.2.4 Special Interfaces, 290\u003c\/p\u003e \u003cp\u003e7.3 Mass Analyzers, 291\u003c\/p\u003e \u003cp\u003e7.3.1 Magnetic Sector, 291\u003c\/p\u003e \u003cp\u003e7.3.2 Quadrupole, 292\u003c\/p\u003e \u003cp\u003e7.3.3 Ion Trap, 293\u003c\/p\u003e \u003cp\u003e7.3.4 Time-of-Flight, 294\u003c\/p\u003e \u003cp\u003e7.3.5 Ft-icr, 295\u003c\/p\u003e \u003cp\u003e7.3.6 Tandem MS, 296\u003c\/p\u003e \u003cp\u003e7.4 Role of Instrumental Parameters on Ionization Efficiency in LC\/MS, 299\u003c\/p\u003e \u003cp\u003e7.4.1 Optimization of Ionization Settings, 299\u003c\/p\u003e \u003cp\u003e7.4.2 Effect of Flow Rate, 302\u003c\/p\u003e \u003cp\u003e7.5 Effect of Mobile-Phase Composition on Ionization Efficiency in LC\/MS, 303\u003c\/p\u003e \u003cp\u003e7.5.1 Choice of Solvents, 303\u003c\/p\u003e \u003cp\u003e7.5.2 Choice of Mobile-Phase Additives, 303\u003c\/p\u003e \u003cp\u003e7.5.3 Adduct Formation, 304\u003c\/p\u003e \u003cp\u003e7.5.4 Effect of Analyte Concentration, 304\u003c\/p\u003e \u003cp\u003e7.5.5 Selected Ion Monitoring and Multiple Reaction Monitoring, 305\u003c\/p\u003e \u003cp\u003e7.6 MS Interpretation, 305\u003c\/p\u003e \u003cp\u003e7.6.1 Molecular Weight and Empirical Formula Determination, 305\u003c\/p\u003e \u003cp\u003e7.6.2 Fragmentation Pattern, 313\u003c\/p\u003e \u003cp\u003e7.7 Practical Applications, 315\u003c\/p\u003e \u003cp\u003e7.7.1 High-Throughput LC\/MS for Combinatorial Chemistry, 315\u003c\/p\u003e \u003cp\u003e7.7.2 Characterization of Impurities and Decomposition Products in Bulk Drug Substances, 317\u003c\/p\u003e \u003cp\u003e7.7.3 Pharmacokinetic Studies of Drugs, 325\u003c\/p\u003e \u003cp\u003e7.7.4 Identification of Drug Metabolites, 332\u003c\/p\u003e \u003cp\u003e7.8 Conclusions, 336\u003c\/p\u003e \u003cp\u003eAcknowledgment, 338\u003c\/p\u003e \u003cp\u003eReferences, 338\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Method Development 347\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction, 347\u003c\/p\u003e \u003cp\u003e8.2 Types of Methods, 348\u003c\/p\u003e \u003cp\u003e8.2.1 Key Raw Materials, 348\u003c\/p\u003e \u003cp\u003e8.2.2 Drug Substance (Active Pharmaceutical Ingredient), 352\u003c\/p\u003e \u003cp\u003e8.2.3 Drug Product, 355\u003c\/p\u003e \u003cp\u003e8.2.4 Achiral Versus Chiral Methods, 359\u003c\/p\u003e \u003cp\u003e8.3 Defining the Method, 360\u003c\/p\u003e \u003cp\u003e8.4 Method Development Considerations, 361\u003c\/p\u003e \u003cp\u003e8.4.1 Sample Properties, 361\u003c\/p\u003e \u003cp\u003e8.4.2 Detector Considerations, 367\u003c\/p\u003e \u003cp\u003e8.4.3 Solution Stability and Sample Preparation, 369\u003c\/p\u003e \u003cp\u003e8.4.4 Choice of Stationary Phase, 373\u003c\/p\u003e \u003cp\u003e8.4.5 Mobile-Phase Considerations, 375\u003c\/p\u003e \u003cp\u003e8.4.6 Gradient Separations, 381\u003c\/p\u003e \u003cp\u003e8.5 Method Development Approaches, 385\u003c\/p\u003e \u003cp\u003e8.5.1 If Analyte Structure Is Known, 385\u003c\/p\u003e \u003cp\u003e8.5.2 If Method Is Being Developed for Separation of Active and Unknown Component, 387\u003c\/p\u003e \u003cp\u003e8.5.3 Defining System Suitability, 389\u003c\/p\u003e \u003cp\u003e8.5.4 Case Study 1: Method Development for a Zwitterionic Compound, 391\u003c\/p\u003e \u003cp\u003e8.5.5 Case Study 2: Influence of pH, Temperature, and Type and Concentration of Solvent on the Retention and Selectivity of Acidic (Phenolic) Compounds, 396\u003c\/p\u003e \u003cp\u003e8.5.6 Case Study 3: Method Development for a Diprotic Basic Compound, 405\u003c\/p\u003e \u003cp\u003e8.5.7 Case Study 4: Structural Elucidation Employing a Deuterated Eluent, 426\u003c\/p\u003e \u003cp\u003e8.6 Effect of pH on UV Absorbance, 429\u003c\/p\u003e \u003cp\u003e8.7 Analyte pK a —From an Analytical Chemist’s Perspective, 432\u003c\/p\u003e \u003cp\u003e8.7.1 Aromatic Acids, 432\u003c\/p\u003e \u003cp\u003e8.7.2 Amines, 434\u003c\/p\u003e \u003cp\u003e8.8 Reversed-Phase Versus Normal-Phase Separations, 435\u003c\/p\u003e \u003cp\u003e8.9 Instrument\/System Considerations, 438\u003c\/p\u003e \u003cp\u003e8.9.1 Column\/System Backpressure, 438\u003c\/p\u003e \u003cp\u003e8.9.2 Column Inlet and Outlet Frits, 439\u003c\/p\u003e \u003cp\u003e8.9.3 Seals, 440\u003c\/p\u003e \u003cp\u003e8.9.4 Mobile-Phase Preparation, 440\u003c\/p\u003e \u003cp\u003e8.9.5 Guard Columns, 441\u003c\/p\u003e \u003cp\u003e8.9.6 Instrument\/System Considerations (Concluding Remarks), 442\u003c\/p\u003e \u003cp\u003e8.10 Column Testing (Stability and Selectivity), 442\u003c\/p\u003e \u003cp\u003e8.10.1 Column Selectivity Testing, 442\u003c\/p\u003e \u003cp\u003e8.10.2 Column Stability Testing, 445\u003c\/p\u003e \u003cp\u003e8.10.3 Choice of Buffer Related to Bonded-Phase Stability, 448\u003c\/p\u003e \u003cp\u003e8.11 Concluding Remarks, 451\u003c\/p\u003e \u003cp\u003eReferences, 452\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Method Validation 455\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRosario LoBrutto and Tarun Patel\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction, 455\u003c\/p\u003e \u003cp\u003e9.2 Validation Report, 457\u003c\/p\u003e \u003cp\u003e9.3 Revalidation, 458\u003c\/p\u003e \u003cp\u003e9.4 Assignment of Validation Parameters, 459\u003c\/p\u003e \u003cp\u003e9.4.1 Accuracy, 460\u003c\/p\u003e \u003cp\u003e9.4.2 Precision, 470\u003c\/p\u003e \u003cp\u003e9.4.3 Linearity, 471\u003c\/p\u003e \u003cp\u003e9.4.4 Lod\/loq, 481\u003c\/p\u003e \u003cp\u003e9.4.5 Relative Response Factors, 484\u003c\/p\u003e \u003cp\u003e9.4.6 Stability of Solution, 485\u003c\/p\u003e \u003cp\u003e9.4.7 Ruggedness\/Robustness, 486\u003c\/p\u003e \u003cp\u003e9.4.8 Specificity, 490\u003c\/p\u003e \u003cp\u003e9.4.9 Forced Degradation Studies (Solid State and Solution)— Drug Substance and Drug Product, 491\u003c\/p\u003e \u003cp\u003e9.5 Distinguishing Drug-Related and Non-Drug-Related Degradation Products, 495\u003c\/p\u003e \u003cp\u003e9.5.1 Drug Product Stress, 497\u003c\/p\u003e \u003cp\u003e9.6 Concluding Remarks, 499\u003c\/p\u003e \u003cp\u003eReferences, 499\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Computer-Assisted HPLC and Knowledge Management 503\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYuri Kazakevich, Michael McBrien, and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction, 503\u003c\/p\u003e \u003cp\u003e10.2 Prediction of Retention and Simulation of Profiles, 504\u003c\/p\u003e \u003cp\u003e10.2.1 General Thermodynamic Basis, 505\u003c\/p\u003e \u003cp\u003e10.2.2 Structure–Retention Relationships, 506\u003c\/p\u003e \u003cp\u003e10.3 Optimization of HPLC Methods, 507\u003c\/p\u003e \u003cp\u003e10.3.1 Off-Line Optimization, 507\u003c\/p\u003e \u003cp\u003e10.3.2 On-Line Optimization, 510\u003c\/p\u003e \u003cp\u003e10.3.3 Method Screening, 511\u003c\/p\u003e \u003cp\u003e10.3.4 Method Optimization, 512\u003c\/p\u003e \u003cp\u003e10.4 Structure-Based Tools, 517\u003c\/p\u003e \u003cp\u003e10.4.1 Knowledge Management, 517\u003c\/p\u003e \u003cp\u003e10.4.2 Applications Databases, 519\u003c\/p\u003e \u003cp\u003e10.4.3 Structure-Based Prediction, 521\u003c\/p\u003e \u003cp\u003e10.5 Conclusion, 528\u003c\/p\u003e \u003cp\u003eReferences, 529\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart II Hplc in the Pharmaceutical Industry 533\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 The Expanding Role of HPLC in Drug Discovery 535\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eDaniel B. Kassel\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction, 535\u003c\/p\u003e \u003cp\u003e11.2 Applications of HPLC\/MS for Protein Identification and Characterization, 536\u003c\/p\u003e \u003cp\u003e11.3 Applications of HPLC\/MS\/MS in Support of Protein Chemistry, 538\u003c\/p\u003e \u003cp\u003e11.4 Applications of HPLC\/MS\/MS in Support of Assay Development and Screening, 539\u003c\/p\u003e \u003cp\u003e11.5 Sources of Compounds for Biological Screening, 540\u003c\/p\u003e \u003cp\u003e11.6 HPLC\/MS Analysis to Support Compound Characterization, 542\u003c\/p\u003e \u003cp\u003e11.6.1 Purity Assessment of Compound Libraries, 544\u003c\/p\u003e \u003cp\u003e11.7 Purification Technologies for Drug Discovery, 547\u003c\/p\u003e \u003cp\u003e11.7.1 UV-Directed Purification, 548\u003c\/p\u003e \u003cp\u003e11.7.2 Mass-Directed Preparative Purification, 549\u003c\/p\u003e \u003cp\u003e11.8 Higher-Throughput Purification Strategies, 552\u003c\/p\u003e \u003cp\u003e11.8.1 Fluorous Split-Mix Library Synthesis and Prepartive LC\/MS De-Mixing, 552\u003c\/p\u003e \u003cp\u003e11.8.2 Parallel Analysis and Parallel Purification, 553\u003c\/p\u003e \u003cp\u003e11.8.3 Streamlining the Purification Process, 558\u003c\/p\u003e \u003cp\u003e11.9 ADME Applications, 559\u003c\/p\u003e \u003cp\u003e11.10 Fast Serial ADME Analyses Incorporating LC-MS and Lc-ms\/ms, 561\u003c\/p\u003e \u003cp\u003e11.10.1 Automated Data Processing Is Instrumental to Achieving High-Throughput ADME, 561\u003c\/p\u003e \u003cp\u003e11.10.2 Enhancing Throughput by Incorporating Pooling Strategies, 563\u003c\/p\u003e \u003cp\u003e11.11 Parallel Approaches to Speeding ADME Analyses, 563\u003c\/p\u003e \u003cp\u003e11.11.1 Nonindexed Parallel Mass Spectrometry, 563\u003c\/p\u003e \u003cp\u003e11.11.2 Indexed (“MUX”) Parallel Mass Spectrometry, 564\u003c\/p\u003e \u003cp\u003e11.12 Automated “Intelligent” Metabolic Stability and Metabolite Id, 565\u003c\/p\u003e \u003cp\u003e11.13 Conclusions, 568\u003c\/p\u003e \u003cp\u003eReferences, 569\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Role of HPLC in Preformulation 577\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eIrina Kazakevich\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction, 577\u003c\/p\u003e \u003cp\u003e12.2 Initial Physicochemical Characterization (Discovery Support), 579\u003c\/p\u003e \u003cp\u003e12.2.1 Ionization Constant, pK a , 580\u003c\/p\u003e \u003cp\u003e12.2.2 Partition and Distribution Coefficients, 582\u003c\/p\u003e \u003cp\u003e12.2.3 Solubility and Solubilization, 586\u003c\/p\u003e \u003cp\u003e12.3 Chemical Stability, 590\u003c\/p\u003e \u003cp\u003e12.4 Salt Selection, 594\u003c\/p\u003e \u003cp\u003e12.5 Polymorphism, 594\u003c\/p\u003e \u003cp\u003e12.6 Preformulation Late Stage (Development Support), 596\u003c\/p\u003e \u003cp\u003e12.7 Conclusions, 599\u003c\/p\u003e \u003cp\u003eReferences, 600\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 The Role of Liquid Chromatography–Mass Spectrometry in Pharmacokinetics and Drug Metabolism 605\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRay Bakhtiar, Tapan K. Majumdar, and Francis L. S. Tse\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction, 605\u003c\/p\u003e \u003cp\u003e13.2 Ionization Processes, 606\u003c\/p\u003e \u003cp\u003e13.3 Tandem-Mass Spectrometry (MS\/MS), 610\u003c\/p\u003e \u003cp\u003e13.4 Sample Preparation Using an Off-Line Approach, 611\u003c\/p\u003e \u003cp\u003e13.4.1 Spe, 612\u003c\/p\u003e \u003cp\u003e13.4.2 Ppt, 613\u003c\/p\u003e \u003cp\u003e13.4.3 Lle, 615\u003c\/p\u003e \u003cp\u003e13.5 Automated Sample Transfer, 615\u003c\/p\u003e \u003cp\u003e13.6 Sample Processing Using an On-Line Approach, 616\u003c\/p\u003e \u003cp\u003e13.7 Matrix Effect and Ion Suppression, 619\u003c\/p\u003e \u003cp\u003e13.8 Regulatory Requirements for LC\/MS Method Validation, 620\u003c\/p\u003e \u003cp\u003e13.9 Ritalin ® : An Application of Enantioselective LC-MS\/MS, 624\u003c\/p\u003e \u003cp\u003e13.10 Gleevec TM (STI571), 626\u003c\/p\u003e \u003cp\u003e13.11 Biomarkers, 629\u003c\/p\u003e \u003cp\u003e13.12 Conclusions, 633\u003c\/p\u003e \u003cp\u003eAcknowledgments, 633\u003c\/p\u003e \u003cp\u003eReferences, 633\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Role of HPLC in Process Development 641\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRichard Thompson and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Responsibilities of the Analytical Chemist During Process Development, 641\u003c\/p\u003e \u003cp\u003e14.2 HPLC Separation Modes, 643\u003c\/p\u003e \u003cp\u003e14.2.1 Reversed-Phase Liquid Chromatography, 643\u003c\/p\u003e \u003cp\u003e14.2.2 Normal-Phase Chromatography, 644\u003c\/p\u003e \u003cp\u003e14.2.3 Sub-\/Supercritical Chromatography, 645\u003c\/p\u003e \u003cp\u003e14.2.4 Hydrophilic Interaction Chromatography, 647\u003c\/p\u003e \u003cp\u003e14.2.5 Ion-Exchange Chromatography, 649\u003c\/p\u003e \u003cp\u003e14.2.6 Chiral Chromatography, 650\u003c\/p\u003e \u003cp\u003e14.3 Sample Preparation, 653\u003c\/p\u003e \u003cp\u003e14.4 HPLC Detectors, 654\u003c\/p\u003e \u003cp\u003e14.5 Method Development, 657\u003c\/p\u003e \u003cp\u003e14.6 In-Process Monitoring, 660\u003c\/p\u003e \u003cp\u003e14.7 Impurity Identification, 663\u003c\/p\u003e \u003cp\u003e14.8 Establishment of HPLC Selectivity by Stress Studies, 665\u003c\/p\u003e \u003cp\u003e14.8.1 Stability in Solution and Forced Degradation Studies (Process Intermediate Compound A), 666\u003c\/p\u003e \u003cp\u003e14.9 HPLC Method Validation, 670\u003c\/p\u003e \u003cp\u003e14.9.1 Prevalidation and System Suitability, 671\u003c\/p\u003e \u003cp\u003e14.9.2 Validation, 672\u003c\/p\u003e \u003cp\u003e14.10 Technology Transfer, 673\u003c\/p\u003e \u003cp\u003e14.11 Concluding Remarks, 674\u003c\/p\u003e \u003cp\u003eReferences, 674\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Role of HPLC During Formulation Development 679\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eTarun S. Patel and Rosario LoBrutto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction, 679\u003c\/p\u003e \u003cp\u003e15.2 Prerequisite for Analytical Chemists During Formulation Development, 681\u003c\/p\u003e \u003cp\u003e15.2.1 Major Degradation Pathways in Pharmaceuticals, 681\u003c\/p\u003e \u003cp\u003e15.3 Properties of Drug Substance, 682\u003c\/p\u003e \u003cp\u003e15.3.1 Solubility of Drug Substance in Presence of Formulation, 682\u003c\/p\u003e \u003cp\u003e15.3.2 Solution Stability, 683\u003c\/p\u003e \u003cp\u003e15.4 Properties of Excipients, 683\u003c\/p\u003e \u003cp\u003e15.5 Impact of Excipients on Degradation of API(s), 684\u003c\/p\u003e \u003cp\u003e15.6 Test Methods for Most Common Dosage Forms in which HPLC Is the Primary Technique, 686\u003c\/p\u003e \u003cp\u003e15.6.1 Assay and Related Substances, 687\u003c\/p\u003e \u003cp\u003e15.6.2 Stability-Indicating Method (SIM), 688\u003c\/p\u003e \u003cp\u003e15.7 Forced Decomposition, 691\u003c\/p\u003e \u003cp\u003e15.8 Compatibility of Excipients with API(s) (Type and Ratio), 695\u003c\/p\u003e \u003cp\u003e15.9 Mass Balance, 698\u003c\/p\u003e \u003cp\u003e15.9.1 Case Study 1, 698\u003c\/p\u003e \u003cp\u003e15.9.2 Case Study 2, 702\u003c\/p\u003e \u003cp\u003e15.9.3 Detection Considerations, 706\u003c\/p\u003e \u003cp\u003e15.9.4 Mass Balance Concluding Remarks, 707\u003c\/p\u003e \u003cp\u003e15.10 Summary of Assay and Related Substances, 707\u003c\/p\u003e \u003cp\u003e15.11 Uniformity of Dosage Units, 707\u003c\/p\u003e \u003cp\u003e15.12 Blend Uniformity (BU), 708\u003c\/p\u003e \u003cp\u003e15.13 Cleaning Verification, 709\u003c\/p\u003e \u003cp\u003e15.14 Extractables\/Leachables, 710\u003c\/p\u003e \u003cp\u003e15.15 Dissolution, 713\u003c\/p\u003e \u003cp\u003e15.16 Method Development, 713\u003c\/p\u003e \u003cp\u003e15.16.1 Sample Preparation Solvent, 714\u003c\/p\u003e \u003cp\u003e15.17 Method Validation, 714\u003c\/p\u003e \u003cp\u003e15.17.1 Completeness of Extraction, 714\u003c\/p\u003e \u003cp\u003e15.18 Testing of Samples, 715\u003c\/p\u003e \u003cp\u003e15.18.1 Clinical Release, 715\u003c\/p\u003e \u003cp\u003e15.18.2 Stability, 715\u003c\/p\u003e \u003cp\u003e15.19 Automation Opportunities, 718\u003c\/p\u003e \u003cp\u003e15.20 Implementation of Alternative Technologies, 719\u003c\/p\u003e \u003cp\u003e15.21 Challenges and Future Trends, 720\u003c\/p\u003e \u003cp\u003eReferences, 720\u003c\/p\u003e \u003cp\u003eA15.1 Addendum (Common Functional Groups), 723\u003c\/p\u003e \u003cp\u003eA15.1.1 Carbonyls, 724\u003c\/p\u003e \u003cp\u003eA15.1.2 Nitrogen Functional Groups, 728\u003c\/p\u003e \u003cp\u003eA15.1.3 Ethers, Thioethers, 730\u003c\/p\u003e \u003cp\u003eA15.1.4 Alkyl\/Aryl Halides, 730\u003c\/p\u003e \u003cp\u003eA15.1.5 Hydroxyls, 731\u003c\/p\u003e \u003cp\u003eA15.1.6 Thiols, 731\u003c\/p\u003e \u003cp\u003eA15.1.7 Phenols, 731\u003c\/p\u003e \u003cp\u003eA15.1.8 Olefins, 731\u003c\/p\u003e \u003cp\u003eA15.1.9 Dimerization, 732\u003c\/p\u003e \u003cp\u003eA15.1.10 Ring Transformations, 733\u003c\/p\u003e \u003cp\u003eAddendum References, 733\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 The Role of HPLC in Technical Transfer and Manufacturing 735\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJoseph Etse\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction, 735\u003c\/p\u003e \u003cp\u003e16.2 Prerequisites for Transfer of HPLC Methods, 736\u003c\/p\u003e \u003cp\u003e16.2.1 Availability of Either Fully or Partially Validated Methods, 736\u003c\/p\u003e \u003cp\u003e16.2.2 Availability of the Finalized Pharmaceutical Active Ingredient (API), Known Degradation Products, By-products and Reference Standards, 738\u003c\/p\u003e \u003cp\u003e16.2.3 Availability of Drug Products Made by the Definitive Manufacturing Process, 739\u003c\/p\u003e \u003cp\u003e16.2.4 Availability of Suitable Instruments and Personnel, 739\u003c\/p\u003e \u003cp\u003e16.2.5 Availability of a Protocol Containing Predetermined Acceptance Criteria, 740\u003c\/p\u003e \u003cp\u003e16.3 Types of Technical Transfer, 745\u003c\/p\u003e \u003cp\u003e16.3.1 From Analytical Research and Development (AR\u0026amp;D) to Quality Control (QC) Lab of the Commercial Organization, 745\u003c\/p\u003e \u003cp\u003e16.3.2 Transfer from AR\u0026amp;D to Another AR\u0026amp;D Organization, 747\u003c\/p\u003e \u003cp\u003e16.3.3 Transfer from AR\u0026amp;D to Contract Research Organization (CRO), 748\u003c\/p\u003e \u003cp\u003e16.4 Different Approaches for Technical Transfer and Manufacturing, 748\u003c\/p\u003e \u003cp\u003e16.4.1 Comparative Testing, 748\u003c\/p\u003e \u003cp\u003e16.4.2 Co-validation of Methods, 750\u003c\/p\u003e \u003cp\u003e16.4.3 Revalidation of Methods, 750\u003c\/p\u003e \u003cp\u003e16.4.4 Waiver of Transfer, 752\u003c\/p\u003e \u003cp\u003e16.5 Potential Pitfalls During Technical Transfer and Manufacturing, 753\u003c\/p\u003e \u003cp\u003e16.5.1 Sample Handling, 753\u003c\/p\u003e \u003cp\u003e16.5.2 Sample Type and Number of Replicate Determination, 755\u003c\/p\u003e \u003cp\u003e16.5.3 Time of Testing, 756\u003c\/p\u003e \u003cp\u003e16.5.4 Instrumental Issues, 757\u003c\/p\u003e \u003cp\u003e16.5.5 Column and Instrumental Issues, 757\u003c\/p\u003e \u003cp\u003e16.5.6 Differences in Chromatographic Data Acquisition Systems, 759\u003c\/p\u003e \u003cp\u003e16.6 Conclusion, 760\u003c\/p\u003e \u003cp\u003eReferences, 760\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart III Hyphenated Techniques and Specialized Hplc Separations 763\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Development of Fast HPLC Methods 765\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAnton D. Jerkovich and Richard V. Vivilecchia\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction, 765\u003c\/p\u003e \u003cp\u003e17.2 Basic Theory, 766\u003c\/p\u003e \u003cp\u003e17.2.1 Resolution and Analysis Time, 767\u003c\/p\u003e \u003cp\u003e17.2.2 Plate Height and Band-Broadening, 769\u003c\/p\u003e \u003cp\u003e17.2.3 Flow Velocity and Column Backpressure, 773\u003c\/p\u003e \u003cp\u003e17.3 Monolithic Columns, 775\u003c\/p\u003e \u003cp\u003e17.3.1 Physical Properties and Preparation of Monolithic Columns, 775\u003c\/p\u003e \u003cp\u003e17.3.2 Chromatographic Properties and Applications of Monolithic Columns, 776\u003c\/p\u003e \u003cp\u003e17.4 Ultra-High-Pressure Liquid Chromatography, 777\u003c\/p\u003e \u003cp\u003e17.4.1 Instrument Considerations when Using Ultra-High Pressures, 779\u003c\/p\u003e \u003cp\u003e17.4.2 Chromatographic Effects of Ultra-High Pressures, 781\u003c\/p\u003e \u003cp\u003e17.4.3 UHPLC Applications, 783\u003c\/p\u003e \u003cp\u003e17.4.4 Method Transfer Considerations, 785\u003c\/p\u003e \u003cp\u003e17.5 Separations on Chips, 786\u003c\/p\u003e \u003cp\u003e17.6 Optimizing Gradient Separations for Speed, 788\u003c\/p\u003e \u003cp\u003e17.6.1 Advantages of Gradient Chromatography, 788\u003c\/p\u003e \u003cp\u003e17.6.2 Optimizing Instrumental Factors, 788\u003c\/p\u003e \u003cp\u003e17.6.3 Basic Parameters Controlling Speed and Resolution, 790\u003c\/p\u003e \u003cp\u003e17.7 Instrumental Requirements for Operating High-Efficiency Columns, 798\u003c\/p\u003e \u003cp\u003e17.7.1 Extra-column Band-Broadening, 798\u003c\/p\u003e \u003cp\u003e17.7.2 Detector Requirements, 802\u003c\/p\u003e \u003cp\u003e17.7.3 Injection Considerations, 804\u003c\/p\u003e \u003cp\u003e17.7.4 Geometric Scaling Relationships, 806\u003c\/p\u003e \u003cp\u003e17.8 Conclusions, 807\u003c\/p\u003e \u003cp\u003eReferences, 807\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Temperature as a Variable in Pharmaceutical Applications 811\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRoger M. Smith\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 The Influence of Temperature on Chromatography, 811\u003c\/p\u003e \u003cp\u003e18.2 Effects on Method Transferability and Reproducibility, 812\u003c\/p\u003e \u003cp\u003e18.3 Elevated Temperature and Pharmaceutical Separations, 813\u003c\/p\u003e \u003cp\u003e18.3.1 Effect of Temperature on Selectivity, 814\u003c\/p\u003e \u003cp\u003e18.3.2 Effect of Temperature on Separation Efficiency, 815\u003c\/p\u003e \u003cp\u003e18.3.3 Other Temperature Effects, 817\u003c\/p\u003e \u003cp\u003e18.3.4 Applications of Elevated Temperatures, 817\u003c\/p\u003e \u003cp\u003e18.4 Superheated Water Chromatography, 821\u003c\/p\u003e \u003cp\u003e18.4.1 Columns for Superheated Water Chromatography, 823\u003c\/p\u003e \u003cp\u003e18.4.2 Detectors in Superheated Water Chromatography, 824\u003c\/p\u003e \u003cp\u003e18.4.3 Pharmaceutical Applications of Superheated Water Chromatography, 824\u003c\/p\u003e \u003cp\u003e18.6 Subambient Separations, 826\u003c\/p\u003e \u003cp\u003e18.7 Conclusion, 830\u003c\/p\u003e \u003cp\u003eReferences, 830\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19 LC\/MS Analysis of Proteins and Peptides in Drug Discovery 837\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eGuodong Chen, Yan-Hui Liu, and Birendra N. Pramanik\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction, 837\u003c\/p\u003e \u003cp\u003e19.2 General Strategies for Analysis of Proteins\/Peptides, 838\u003c\/p\u003e \u003cp\u003e19.2.1 HPLC Methods in Proteins\/Peptides, 838\u003c\/p\u003e \u003cp\u003e19.2.2 MS Methods for Protein Characterization, 843\u003c\/p\u003e \u003cp\u003e19.3 Applications for Biotechnology Products and Drug Targets, 845\u003c\/p\u003e \u003cp\u003e19.3.1 Biotechnology Products Development, 845\u003c\/p\u003e \u003cp\u003e19.3.2 Protein Glycosylation and Phosphorylation, 860\u003c\/p\u003e \u003cp\u003e19.3.3 Microwave-Assisted Methods for Proteins\/Peptides, 871\u003c\/p\u003e \u003cp\u003e19.3.4 Drug–Protein Interaction by Affinity-Based Hplc\/ms, 877\u003c\/p\u003e \u003cp\u003e19.3.5 Multidimensional HPLC in Proteomics, 879\u003c\/p\u003e \u003cp\u003e19.3.6 Characterization of Adenovirus Structural Proteins for Gene Therapy, 884\u003c\/p\u003e \u003cp\u003e19.4 Conclusions, 890\u003c\/p\u003e \u003cp\u003eAcknowledgment, 890\u003c\/p\u003e \u003cp\u003eReferences, 890\u003c\/p\u003e \u003cp\u003e\u003cb\u003e20 LC-NMR Overview and Pharmaceutical Applications 901\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMaria Victoria Silva Elipe\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction, 901\u003c\/p\u003e \u003cp\u003e20.2 Historical Background of NMR, 902\u003c\/p\u003e \u003cp\u003e20.2.1 Historical Development of NMR, 902\u003c\/p\u003e \u003cp\u003e20.2.2 Historical Development of LC-NMR, 904\u003c\/p\u003e \u003cp\u003e20.3 Lc-nmr, 905\u003c\/p\u003e \u003cp\u003e20.3.1 Introduction, 905\u003c\/p\u003e \u003cp\u003e20.3.2 Modes of Operation for LC-NMR, 908\u003c\/p\u003e \u003cp\u003e20.3.3 Other Analytical Separation Techniques Hyphenated with NMR, 914\u003c\/p\u003e \u003cp\u003e20.3.4 Applications of LC-NMR, 916\u003c\/p\u003e \u003cp\u003e20.4 LC-MS-NMR (or LC-NMR-MS or LC-NMR\/MS), 916\u003c\/p\u003e \u003cp\u003e20.4.1 Introduction, 916\u003c\/p\u003e \u003cp\u003e20.4.2 Modes of Operation for LC-MS-NMR, 917\u003c\/p\u003e \u003cp\u003e20.4.3 Applications of LC-MS-NMR, 926\u003c\/p\u003e \u003cp\u003e20.5 Conclusions, 926\u003c\/p\u003e \u003cp\u003eAcknowledgments, 927\u003c\/p\u003e \u003cp\u003eReferences, 927\u003c\/p\u003e \u003cp\u003e\u003cb\u003e21 Trends in Preparative HPLC 937\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eErnst Kuesters\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21.1 Introduction, 937\u003c\/p\u003e \u003cp\u003e21.2 Method Development in Preparative HPLC, 939\u003c\/p\u003e \u003cp\u003e21.2.1 Optimization of Selectivity, 940\u003c\/p\u003e \u003cp\u003e21.2.2 Scale-Up of Analytical Methods, 941\u003c\/p\u003e \u003cp\u003e21.2.3 Adsorption Isotherms and Their Determination, 946\u003c\/p\u003e \u003cp\u003e21.3 Columns and Stationary Phases, 951\u003c\/p\u003e \u003cp\u003e21.3.1 Stationary Phases, 951\u003c\/p\u003e \u003cp\u003e21.3.2 Particle Size, Shape, and Distribution, 954\u003c\/p\u003e \u003cp\u003e21.3.3 Columns and Packing Procedures, 954\u003c\/p\u003e \u003cp\u003e21.4 Choice of Preparative LC Technology, 955\u003c\/p\u003e \u003cp\u003e21.4.1 Classical Batch Elution, 956\u003c\/p\u003e \u003cp\u003e21.4.2 Recycling Chromatography, 956\u003c\/p\u003e \u003cp\u003e21.4.3 Displacement Chromatography, 959\u003c\/p\u003e \u003cp\u003e21.4.4 Simulated Moving Bed Chromatography, 962\u003c\/p\u003e \u003cp\u003e21.5 Detection Tools, 975\u003c\/p\u003e \u003cp\u003e21.5.1 On-Line HPLC Detection, 975\u003c\/p\u003e \u003cp\u003e21.5.2 Preparative HPLC-MS, 977\u003c\/p\u003e \u003cp\u003e21.6 Conclusion, 978\u003c\/p\u003e \u003cp\u003eAcknowledgments, 980\u003c\/p\u003e \u003cp\u003eReferences, 980\u003c\/p\u003e \u003cp\u003e\u003cb\u003e22 Chiral Separations 987\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eNelu Grinberg, Thomas Burakowski, and Apryll M. Stalcup\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e22.1 Introduction, 987\u003c\/p\u003e \u003cp\u003e22.1.1 Enantiomers, Diastereomers, Racemates, 988\u003c\/p\u003e \u003cp\u003e22.2 Separation of Enantiomers Through the Formation of Diastereomers, 989\u003c\/p\u003e \u003cp\u003e22.2.1 Mechanism of Separation, 990\u003c\/p\u003e \u003cp\u003e22.2.2 General Concepts for Derivatization of Functional Groups, 991\u003c\/p\u003e \u003cp\u003e22.3 Molecular Interactions, 992\u003c\/p\u003e \u003cp\u003e22.3.1 The Probability of Molecular Interactions, 992\u003c\/p\u003e \u003cp\u003e22.3.2 The Types of Molecular Interactions, 995\u003c\/p\u003e \u003cp\u003e22.3.3 Chiral Separation Through Hydrogen Bonding, 995\u003c\/p\u003e \u003cp\u003e22.3.4 Chiral Separation Through Inclusion Compounds, 1002\u003c\/p\u003e \u003cp\u003e22.3.5 Charge Transfer, 1011\u003c\/p\u003e \u003cp\u003e22.4 Mixed Types of Interaction, 1018\u003c\/p\u003e \u003cp\u003e22.4.1 Polysaccharide Phases, 1019\u003c\/p\u003e \u003cp\u003e22.4.2 Antibiotic Phases, 1022\u003c\/p\u003e \u003cp\u003e22.4.3 Protein Phases, 1026\u003c\/p\u003e \u003cp\u003e22.5 Ligand Exchange, 1030\u003c\/p\u003e \u003cp\u003e22.6 Chiral Mobile Phases, 1032\u003c\/p\u003e \u003cp\u003e22.6.1 Chiral Mobile-Phase Retention Mechanisms, 1032\u003c\/p\u003e \u003cp\u003e22.6.2 Selectivity with Chiral Mobile-Phase Additives, 1035\u003c\/p\u003e \u003cp\u003e22.6.3 Chiral Additives with Chiral Stationary Phases, 1035\u003c\/p\u003e \u003cp\u003e22.6.4 Interactions with Chiral Mobile Phases, 1037\u003c\/p\u003e \u003cp\u003e22.7 Method Development for Chiral Separation, 1038\u003c\/p\u003e \u003cp\u003e22.8 Concluding Remarks, 1040\u003c\/p\u003e \u003cp\u003eReferences, 1041\u003c\/p\u003e \u003cp\u003eChemical and Drug Compound Index 1053\u003c\/p\u003e \u003cp\u003eSubject Index 1061\u003c\/p\u003e\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003eSubject Areas: Chemistry [\u003ca title=\"See our other books on Chemistry\" href=\"https:\/\/freshlyprintedbooks.co.uk\/search?q=%22Chemistry%20%5BPN%5D%22\"\u003ePN\u003c\/a\u003e]\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\u003c\/font\u003e","brand":"Wiley-Interscience","offers":[{"title":"Brand New","offer_id":52405526233368,"sku":"9780471681625","price":186.29,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0730\/2037\/5320\/files\/9780471681625.jpg?v=1784136176","url":"https:\/\/freshlyprintedbooks.co.uk\/products\/hplc-for-pharmaceutical-scientists-hardback-9780471681625","provider":"Freshly Printed Books","version":"1.0","type":"link"}