Tandem Mass Spectrometry in Pediatrics
Key Points
- Gold standard for metabolic screening
- Enables simultaneous multi-analyte detection
- High sensitivity and specificity
- Rapid turnaround time
- Cost-effective screening method
Technical Principles
Basic Components
- Ion Source
- Electrospray Ionization (ESI)
- Atmospheric Pressure Chemical Ionization (APCI)
- Matrix-Assisted Laser Desorption/Ionization (MALDI)
- Electron Impact (EI)
- Mass Analyzers
- Quadrupole Mass Filter
- Mass selection
- Ion focusing
- Transmission efficiency
- Collision Cell
- Fragmentation process
- Collision energy optimization
- Fragment ion generation
- Detection System
- Ion detection
- Signal amplification
- Data acquisition
- Quadrupole Mass Filter
Clinical Applications
Newborn Screening
- Amino Acid Disorders
- Phenylketonuria
- Maple syrup urine disease
- Homocystinuria
- Tyrosinemia
- Fatty Acid Oxidation Disorders
- Medium-chain acyl-CoA dehydrogenase deficiency
- Long-chain hydroxyacyl-CoA dehydrogenase deficiency
- Carnitine uptake defects
- Very long-chain acyl-CoA dehydrogenase deficiency
- Organic Acid Disorders
- Methylmalonic acidemia
- Propionic acidemia
- Isovaleric acidemia
- Glutaric acidemia type I
Therapeutic Drug Monitoring
- Drug Classes
- Immunosuppressants
- Tacrolimus
- Cyclosporine
- Sirolimus
- Antiepileptics
- Carbamazepine
- Phenytoin
- Valproic acid
- Antibiotics
- Aminoglycosides
- Vancomycin
- Immunosuppressants
Analytical Methods
Sample Preparation
- Specimen Types
- Dried blood spots
- Plasma/serum
- Urine
- Cerebrospinal fluid
- Extraction Methods
- Liquid-liquid extraction
- Solid-phase extraction
- Protein precipitation
- Derivatization techniques
Quality Control
Analytical Parameters
- Method Validation
- Linearity assessment
- Precision studies
- Accuracy verification
- Detection limits
- Reference intervals
- Quality Assurance
- Internal controls
- External quality assessment
- Proficiency testing
- Method comparison
Result Interpretation
Data Analysis
- Quantitative Analysis
- Calibration curves
- Internal standards
- Matrix effects
- Ion suppression
- Clinical Interpretation
- Reference ranges
- Age-specific cutoffs
- Disease patterns
- Follow-up recommendations
Advanced Applications
Emerging Technologies
- High-Resolution MS
- Untargeted metabolomics
- Novel biomarker discovery
- Structural characterization
- Ion Mobility MS
- Isomer separation
- Conformational analysis
- Complex mixture analysis
Clinical Implementation
Workflow Integration
- Laboratory Setup
- Equipment requirements
- Staff training
- Standard operating procedures
- Result reporting
- Clinical Protocols
- Screening algorithms
- Confirmatory testing
- Follow-up procedures
- Emergency protocols
Limitations and Challenges
- Technical Considerations
- Matrix effects
- Ion suppression
- Interference
- Carryover
- Clinical Limitations
- False positives
- False negatives
- Result interpretation
- Cost considerations
