Profiling and in vivo Quantification of Proteins by High Resolution Mass Spectrometry: The Example of Goserelin, an Analogue of Luteinizing Hormone-Releasing Hormone
-
Sophie Michalet
Abstract
Proteins are essential biomolecules which are frequently involved in major pathological syndromes and are widely used as diagnostic markers or therapeutic agents. The emergence of proteomics will doubtless further increase the significance of proteins both in the clinic and in the life sciences in general. Our main objective is to offer innovative solutions to what we like to call the “post-proteomics era”. To achieve our goal, we intend to develop novel approaches and technologies for in vivo metabolic studies of proteins using mass spectrometry (MS), focusing on pharmacokinetics and pharmacodynamics. Using goserelin as a model, we have successfully developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of an intact analogue of luteinizing hormone-releasing hormone (LHRH) in small volumes of rat plasma samples at concentrations ranging from 0.3 to 405.0 μg/l. To this end, a microbore reversed-phase-HPLC system was coupled on-line to a tandem high resolution quadrupole time-of-flight (Q-TOF) instrument fitted with an electrospray ion source and operated in LC-MS/MS mode. External calibration was used and the high resolution was crucial to discard contaminating signals, which would not have been possible with the more conventional triple quadrupole mass spectrometers operated in a static mode. For low sample amounts, calibration curves were constructed corresponding to rat plasma levels of 0.3 to 16.4 μg/l and found to be of third order with a coefficient of determination greater than 0.999. The relative standard deviation was found to be lower than 15%. A lower limit of detection (LLOD) of 0.17 μg/l and a lower limit of quantification (LLOQ) of 0.3 μg/l were determined.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Mass Spectrometry in Laboratory Medicine
- Mass Spectrometry-Based Proteomics: Current Status and Potential Use in Clinical Chemistry
- Application of Gas Chromatography-Mass Spectrometry for Analysis of Isoprostanes: Their Role in Cardiovascular Disease
- The Application of Clinical Proteomics to Cancer and other Diseases
- Therapeutic Drug Monitoring of 13 Antidepressant and Five Neuroleptic Drugs in Serum with Liquid Chromatography-Electrospray Ionization Mass Spectrometry
- Mass Spectrometric Analysis of Human Transferrin in Different Body Fluids
- Profiling and in vivo Quantification of Proteins by High Resolution Mass Spectrometry: The Example of Goserelin, an Analogue of Luteinizing Hormone-Releasing Hormone
- Determination of Nicotine and Its Major Metabolite Cotinine in Plasma or Serum by Gas Chromatography-Mass Spectrometry Using Ion-Trap Detection
- Analysis of Nitrofuran Metabolites in Food by High-Performance Liquid Chromatography with Tandem Mass Spectrometry Detection
- Automated LC-MS Method for the Fast Stereoselective Determination of Methadone in Plasma
- Proteome Analysis of Diseased Joints from Mice Suffering from Collagen-Induced Arthritis
- Quantitative Analysis of Bile Acids in Human Plasma by Liquid Chromatography-Electrospray Tandem Mass Spectrometry: A Simple and Rapid One-Step Method
- Organic Acids in the Second Morning Urine in a Healthy Swiss Paediatric Population
- Acknowledgement
- Meetings and Awards
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Mass Spectrometry in Laboratory Medicine
- Mass Spectrometry-Based Proteomics: Current Status and Potential Use in Clinical Chemistry
- Application of Gas Chromatography-Mass Spectrometry for Analysis of Isoprostanes: Their Role in Cardiovascular Disease
- The Application of Clinical Proteomics to Cancer and other Diseases
- Therapeutic Drug Monitoring of 13 Antidepressant and Five Neuroleptic Drugs in Serum with Liquid Chromatography-Electrospray Ionization Mass Spectrometry
- Mass Spectrometric Analysis of Human Transferrin in Different Body Fluids
- Profiling and in vivo Quantification of Proteins by High Resolution Mass Spectrometry: The Example of Goserelin, an Analogue of Luteinizing Hormone-Releasing Hormone
- Determination of Nicotine and Its Major Metabolite Cotinine in Plasma or Serum by Gas Chromatography-Mass Spectrometry Using Ion-Trap Detection
- Analysis of Nitrofuran Metabolites in Food by High-Performance Liquid Chromatography with Tandem Mass Spectrometry Detection
- Automated LC-MS Method for the Fast Stereoselective Determination of Methadone in Plasma
- Proteome Analysis of Diseased Joints from Mice Suffering from Collagen-Induced Arthritis
- Quantitative Analysis of Bile Acids in Human Plasma by Liquid Chromatography-Electrospray Tandem Mass Spectrometry: A Simple and Rapid One-Step Method
- Organic Acids in the Second Morning Urine in a Healthy Swiss Paediatric Population
- Acknowledgement
- Meetings and Awards
