Quantitative Applications of Mass Spectrometry

Professor Pietro Traldi, Research Executive, National Council of Research, CNR, ISTM Corso Stati Uniti 4 I35127 Padova, Italy Fields of interest include structure and reactivity of gaseous ions; -MS application in environmental and biomedical fields; Development of new analytical methods; Instrumental developments. Pietro Traldi is author of over 500 publications on international journals; he is member of the advisory boards of JMS, MSR, RCM and EMS. He is the promoter and the chairman of the Informal Meeting of Mass Spectrometry. Professor Irma Lavagnini, Associate Professor in Analytical Chemistry, Faculty of Pharmacy. Scientific research focus is Chemical data handling Professor Franco Magno, Padua University, Italy, Full Professor of Analytical Chemistry since 1980. Main research areas in electroanalytical techniques; Development and application of the digital simulation techniques to rationalize voltammetric responses; Development and optimization of analytical procedures to determine species of relevant enviromental and/or industrial interest. Dr Roberta Seraglia, National Council of Research, Padova, Italy, Researcher of CNR, Institute of Molecular Sciences and Technologies, Padova. 130 papers published in International Journals and 160 communications at International and National congresses.

Preface ix

Acknowledgements xi

Introduction xiii

1 What Instrumental Approaches are Available 1

1.1 Ion Sources 1

1.1.1 Electron Ionization 3

1.1.2 Chemical Ionization 4

1.1.3 Atmospheric Pressure Chemical Ionization 6

1.1.4 Electrospray Ionization 8

1.1.5 Atmospheric Pressure Photoionization 11

1.1.6 Matrix-assisted Laser Desorption/Ionization 12

1.2 Mass Analysers 14

1.2.1 Mass Resolution 14

1.2.2 Sector Analysers 15

1.2.3 Quadrupole Analysers 19

1.2.4 Time-of-flight 25

1.3 GC/MS 27

1.3.1 Total Ion Current (TIC) Chromatogram 27

1.3.2 Reconstructed Ion Chromatogram (RIC) 28

1.3.3 Multiple Ion Detection (MID) 29

1.4 LC/MS 29

1.5 MS/MS 30

1.5.1 MS/MS by Double Focusing Instruments 30

1.5.2 MS/MS by Triple Quadrupoles 31

1.5.3 MS/MS by Ion Traps 32

1.5.4 MS/MS by Q-TOF 34

References 34

2 How to Design a Quantitative Analysis 37

2.1 General Strategy 38

2.1.1 Project 41

2.1.2 Sampling 41

2.1.3 Sample Treatment 42

2.1.4 Instrumental Analysis 43

2.1.5 Method Validation 53

References 53

3 How to Improve Specificity 55

3.1 Choice of a Suitable Chromatographic Procedure 56

3.1.1 GC/MS Measurements in Low and High Resolution Conditions 56

3.1.2 LC/ESI/MS and LC/APCI/MS Measurements 61

3.2 Choice of a Suitable Ionization Method 79

3.3 An Example of High Specificity and Selectivity Methods: The Dioxin Analysis 85

3.3.1 Use of High Resolution MID Analysis 85

3.3.2 NICI in the Analysis of Dioxins, Furans and PCBs 93

3.3.3 MS/MS in the Detection of Dioxins, Furans and PCBs 95

3.4 An Example of MALDI/MS in Quantitative Analysis of Polypeptides: Substance P 101

References 106

4 Some Thoughts on Calibration and Data Analysis 107

4.1 Calibration Designs 108

4.2 Homoscedastic and Heteroscedastic Data 108

4.2.1 Variance Model 109

4.3 Calibration Models 109

4.3.1 Unweighted Regression 109

4.3.2 Weighted Regression 119

4.3.3 A Practical Example 126

4.4 Different Approaches to Estimate Detection and Quantification Limits 130

References 132

Index 135