MSACL Conference Schedule

High Throughput Quantitative Analysis of Acylcarnitines and Amino Acids by MADI-Triple Quadrupole Mass Spectrometry
Tue 10:00 AM - Session: Inborn Errors in Metabolism
Jay Corr
Electrospray (ESI) triple quadrupole mass spectrometry is routinely used in a number of newborn screening laboratories around the world. This rapid technique provides the sensitivity, selectivity, precision and accuracy to allow high throughput screening for a number of inborn errors of metabolism. Quantitative analysis of acylcarnitines and amino acids from dried blood spots of neonates typically takes 1 to 2 minutes for screening for a number of fatty acid oxidation disorders, organic acidemias, and amino acid acidemias. This paper describes a new, higher throughput mass spectrometry technique using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry on a triple quadrupole mass spectrometer (MALDI-QqQ). This technique permits analyses to be performed in times ranging from 1 to 10 seconds, depending on the exact analyses, with no danger of sample carry-over.

In this new technique samples are mixed with a MALDI matrix (a UV light absorbing compound) and deposited in specific locations on a MALDI target plate. The samples are irradiated by a series of UV laser pulses from a high repetition rate laser (1 kHz), causing them to be desorbed and ionized, for subsequent analysis by the triple quadrupole mass spectrometer. The Multiple Reaction Monitoring (MRM) mode of operation of the mass spectrometer permits measurement of numerous MS/MS precursor/product ion pairs (usually associated with the butyl esters of acylcarnitines or amino acids) as the laser rapidly rasters across the MALDI target plate. The analyst may select to perform quantitation on as many MRM ion pairs as they wish, effectively selecting the ions of interest which would be monitored in neutral loss or precursor scans. The usual precursor and neutral loss scans may be also performed, and will be demonstrated.

The potential of the technique for newborn screening will be demonstrated through data acquired with an Applied Biosystems/MDS Analytical Technologies FlashQuant