Contents. List of Contributors. Structure of the Book. Part 1 Evaluation and Estimation of Chromatographie Data 1

Transcription

1 Contents Preface XIII List of Contributors XV Structure of the Book XVII Part 1 Evaluation and Estimation of Chromatographie Data 1 1 Evaluating Chromatograms 3 Hans-Joachim Kuss and Daniel Stauffer 1.1 Efficiency EMG Model Chromatogram Selectivity 8 References 8 2 Integration Parameters 9 Daniel Stauffer and Hans-Joachim Kuss 2.1 Peak Recognition Methods The Classical Method Alternative Method Integration and Integration Parameters Data Acquisition and Integration with Empower Data Acquisition and Integration with Chromeleon Data Acquisition and Integration with EZChrom Elite A Data Recording and Integration with ChemStation 16 3 Integration Errors 17 Hans-Joachim Kuss 3.1 What Does the Literature Say on Integration Errors? Integration in Routine Practice 19 Bibliografische Informationen digitalisiert durch

2 VI Contents Integration, Simple and Automatically Feasible? Comparison of Integration Systems with a Small Number of Tall Peaks Comparison of Integration Systems for Numerous Small Peaks Chromatogram Simulation Simulation of a Digital Chromatogram One Peak Several Peaks Noise Drift Peak Area Peaks Merged Together Unclear Baseline Tailing Data Point Interval Other Characteristic Quantities Gas Chromatogram Applications of the Simulation Simulation of a Standard Curve Tenfold Simulation at the limit of Quantification Simulation of an Isocratic Chromatogram Simulation of a Gradient Chromatogram By-Product Analysis Post-Simulation of Real Chromatograms 78 References 82 4 Simulation of Chromatograms 83 Uwe D. Neue 4.1 Introduction Peak Simulation Symmetrical Peaks Peak Tailing The Baseline The Chromatogram Simple Retention Modeling and Real Chromatograms Isocratic Chromatography Gradient Chromatography Outlook 102 References Integration of Asymmetric Peaks 105 Hans-Joachim Kuss 5.1 The Valley Between Merged Peaks Small Peak Between Larger Ones Peak Pairs 112

3 Contents VII 5.4 Simulation of a Calibration Exponential Skim Integration of Merged Peaks Integration in Daily Practice 121 References Deconvolution 123 Mike Hillebrand 6.1 Introduction Software Applications for Deconvolution Influences on Deconvolution The Baseline Path Peak Homogeneity - Number of Peaks Noise Peak Symmetry Deconvolution of Gaussian-Shaped Peaks Westerberg Report Simulation Deconvolution of Peaks with Tailing Peaks with Different Tailing Deconvolution of Gradient Runs Complex Baseline Real Chromatogram Outlook 149 References Interpretation of Chromatograms 153 Hans-Joachim Kuss 7.1 Using the Peak Height Evaluation Evaluation Methods Calibration Linear Regression Weighted Linear Regression 361 References General Interpretation of Analytical Data 167 Joachim Ermer 8.1 (Normal) Distribution of Analytical Data Problems of Prediction Analytical Variability Variability Contributions and Precision Levels System or Injection Precision Repeatability Reproducibility Number of Series 180

4 VIII Contents Analysis of Variances Benchmarking for Reproducibility Consequences for the Design of an Analytical Procedure Concentration Dependence of the Precision Conclusions Key Points 188 References Metrological Aspects of Chromatographie Data Evaluation 191 Ulrich Panne 9.1 Introduction Measurement Uncertainty Traceability of Analytical Measurements 205 References 208 Part 2 Characterization of the Evaluation of Different Chromatographie Modes Evaluation and Estimation of Chromatographie Data in CC 213 Werner Engewald (Translator. Mike Hillebrand) 10.1 Introduction How Does GC Differ from HPLC? What Consequences Result from These Differences? Applicability of GC Sample Injection Column Detector Fast Gas Chromatography Qualitative Analysis Introductory Remarks Fingerprint Analysis Peak Purity Comparison of Retention Times Relative Retention Times Retention Time Locking (RTL) GC-MS Coupling MS as an Identifying Detector (Scan Mode) Use of Spectral Libraries Spectrum Deconvolution MS as a Mass-Selective Detector Mass Fragmentography (Reconstructed or Extracted Ion Chromatogram) SIM (Single Ion Monitoring) or MID (Multiple Ion Recording) Chemical Ionization 235

5 Contents IX 10.5 Quantitative Analysis Setting up an Analysis Sequence Isotope Dilution Analysis (IDA) or Stable Isotope Dilution Analysis (SIDA) Matrix Effects in Trace Analysis Headspace-GC Estimation of the Correction Factor with the FID 239 References Data Evaluation in LC-MS 243 Hartmut Kirchherr 11.1 Introduction Influence of the Matrix in Chromatography Internal Standards Adjustments to the Mass Spectrometer Evaluation Software 258 References Evaluation of Chromatographie Data in Ion Chromatography 261 Heiko Herrmann and Detlef Jensen 12.1 Introduction Eluents Purity The Water Dip - the Solvent Peak in Ion Chromatography Contaminants Calibration Functions 268 References Qualification of CPC/CFC/SEC Data and Results 271 Daniela Held and Peter KHz 13.1 Introduction Principles of GPC/SEC Data Processing Calculation of Molar Mass Averages Guidelines, Standards and Requirements for GPC/SEC Data Processing Validation and Tests for GPC/SEC Data Evaluation Description of a General Verification Procedure for GPC/SEC Software Validation of the Molar Mass Distribution Calculation Influence of Data Processing, Calibration Methods and Signal Quality on Accuracy and Precision of GPC/SEC Results Validation of GPC/SEC Evaluation with External Molar Mass Calibration Validation of GPC/SEC Evaluation with Viscometry Set-ups 285

6 X Contents Influence of Detector Noise on the Accuracy of GPC/SEC Results Influence of the Detector Drift on the Accuracy of GPC/SEC Results Influence of the Number of Data Points on the Accuracy of GPC/SEC Results Influence of GPC/SEC Specific Parameters on the Precision and Accuracy of GPC/SEC Results Influence of Parameters for GPC/SEC with External Molar Mass Calibration Influence of the Calibration Curve Influence of Instrument Parameters (Instrument Performance) Influence of Evaluation Parameters Influence of Parameters for GPC/SEC with light Scattering Detection Influence of Instrument Calibration Influence of Instrument Performance Influence of Evaluation Parameters Repeatability and Reproducibiliry of G PC/S EC Analyses Summary 301 References 302 Part 3 Requirements for Chromatographie Data Analysis from the Viewpoint of Organisations and Public Authorities The Science Behind the Pharmaceutical Regulatory Chromatographie Procedures 305 Linda Ng 14.1 Introduction Instrument Qualification Chromatographie Procedures Method Design, Development and Validation Compendial Procedures Conclusions 331 References Interpretation of Chromatographie Data According to the Pharmacopoeias - Control of Impurities 313 Ulrich Rose 15.1 Outline Interpretation of Qualitative Data System Suitability Test Interpretation of Quantitative Data 318 References 320

7 Contents XI 16 Requirements of (Chromatographie) Data in Pharmaceutical Analysis 321 Joachim Ermer 16.1 System Suitability Tests European Pharmacopoeia (EP) Chromatographie Parameters Signal-to-Noise Ratio System Precision US Pharmacopoeia FDA Reviewer Guidance Acceptance Limits for the Specification and Precision Assay Based on the Method Capability Index Based on the 95% Prediction Interval (DPhG-Approach) Impurity Determination Acceptance Limits of the Specification Quantitation Limit and Variability Key Points Interpretation and Treatment of Analytical Data Prerequisites Measurement Principles and Variation Outlying Results Outlier Test According to Hampel Comparison of Analytical Results Precision Accuracy Key Points 338 References Evaluation and Valuation of Chromatographie Data 341 Stavros Kromidas 17.1 Introduction The Situation - or Why Does so Little Change? How Can Something Change and When is it Really Necessary? Who Can Change Something? 345 Index 347 Contents of the CD 357