R. Lord
October 4, 2011
Advantages of LC/MS-MS Over GC/MS for Organic Acid Profiles
Summary Table
Aspect
Sample prep.
-
Details
Chromatographic
flexibility
Detector specificity
Overall variability
Run time
Instrument cost
LC/MS-MS
GC/MS
Minimal – low variability; high
recovery
Dilute urine into injection vial
containing solution with
appropriate internal standards
and inject on LC/MS-MS.
Extensive – high variability; low
recovery
Acidify urine; Extract organic
acids into non-polar solvent*;
Derivitize keto groups*;
Derivitize all other functional
groups (hydroxyl, carboxylic
acid, amine, thiol, phosphate)*;
Reduce volume and transfer to
GC/MS injection vial*; Inject on
GC/MS
* steps contributing to variable
analyte recoveries
Limited – all analytes must be
volatilized; limited choices of
stationary phases
Great – analytes may be
grouped by optimal resolution
conditions for parallel runs on
multiple instruments; highresolution chiral separations
Great due to tandem
ionization conditions and
multiple ion
transition settings
Low
5-20 min
High
Limited to daughter ion
selection without parent ion
identification
High
> 40 min
Moderate
RUGGED
Performing large profile analysis of urinary organic acids is a complex challenge for
clinical laboratories. The ultimate requirement is to achieve rugged, reliable assays of each of the 40 or
more analytes reported. That means the methods must deliver high accuracy under conditions of heavy
volume independent of the operator.
RELIABLE
The ultimate criteria for success are low variability with high flexibility in assay
conditions. The flexibility requirement is important because of the highly variable chemical nature of the
various compounds to be measured. Low variability means that the accurate results are produced
routinely. The combination of these dual requirements is achieved much more effectively by using
LC/MS-MS than GC/MS.
ACCURATE
This critical improvement derives from the far simpler sample preparation in LC/MS-MS
technology that insures 100% recoveries of all analytes. This greatly reduces the overall variability of the
assays yielding more consistent and accurate results with greater sensitivity and specificity.