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GC & GC/MS Method Development Quick Reference Guide
This GC & GC/MS guide offers practical advice which we hope will assist users
avoid many common problems encountered from the results of poor method de-
velopment, translation or optimisation. This can range from inaccurate results to
instruments with significant downtime and high maintenance costs. The objective
being to develop automated reliable identification and quantitative results that are
fit for purpose.
Conclusion
If these guidelines are adhered to you will avoid undesirable outcomes and have a fully
utilized robust method providing accurate and reliable results fit for purpose.
ChromSolutions Ltd
What we offer at ChromSolutions is our wealth of experience in analytical instrument sales
and support (over 110 years distributed through the members of our company). We can
help you from defining your requirements to the implementation of a robust
analytical method fit for purpose.
For more information on GC/MS method development please contact us:
Before Commencement
• Ensure the new or existing instrument is configured and installed with the cor-
rect supplies, gases, column(s) and injector(s), valve(s), liner(s), detector, inter-
faces and software options for detection of the target analytes.
• The instrument has been installed to manufactures specification and all
maintenance logs/service history are current up to date.
Initial Testing
• Ensure data capture method has sufficient speed to comply with accuracy
requirement (8 points min across a peak for 5-10% repeatability).
• Adjust column flows and oven temperature profile to achieve the required
sample throughput and separation for a mid range standard.
• Optimise detector conditions for best response and minimal interference.
• Optimise injector parameters for best response, chromatographic resolution
and minimal peak distortion.
• Apply data processing method to obtain the correct integration parameters
and identification windows for the chromatography.
• Adjust auto sampler settings and to obtain optimal repeatability (min 6 injec-
tions) on a mid range standard.
• If the method criteria cannot be reached for the mid range standard consider
increasing data capture speed and/or the addition of internal standard(s).
SQC & Sample Testing
• Inject a matrix matched standard or a sample (min 6 injections) to check identifica-
tion, integration and repeatability.
• If the chromatograms/results differ significantly from the initial testing or than ex-
pected/acceptable, consider a more appropriate matrix elimination strategy.
Carry Over Testing
• Inject high std +20% followed by a blank and measure carry over and carry over re-
peatability. Also ensuring overloaded peak shapes is kept to a minimum.
• Modify auto sampler parameters and wash solvents/purge gas to minimise carry
over.
• Modify data processing method to ensure correct integration of high level standard
and blanks.
• Run a sample or independent QC standard six times with new auto sampler condi-
tions to compare chromatography and repeatability data to the initial SQC and sam-
ple testing. If not comparable re-adjust modifications made in carry over tests.
Calibration/QC/Validation Considerations
• Initial Calibration for external/internal standard and mole %/normalised %.
• Run calibration range from low std 3 * limit of detection and top std max level +20%
(ideally 7 point). Run 3 points at each level, 6 points at LOQ, 6 points at mid point
and 6 points at highest level. Plot calibration curve and assess linearity criteria and
calculate % rsd at levels containing 6 points.
• If any adjustments are made to the method the sample or independent QC/sample
spikes need to be recalculated or re-injected.
• Devise a QC/validation protocol with independent QC and calibrations to ensure
method robustness and the control of the frequency of the maintenance procedures.
Typical protocols include injection of low and high level standards/SQC’s/sample
spikes measuring peak areas, retention times and peak shapes. In addition baseline
noise and offsets from chromatogram start and end are typically measured.
C3 - C15 Hydrocarbons Method Translation Example
Analytes
1 Propane
2 n-Butane
3 n-Pentane
4 Hexane
5 Benzene
6 Cyclohexane
7 Heptane
8 Toluene
9 Octane
10 Ethylbenzene
11 Nonane
12 o-Xylene
13 Decane
14 Undecane
15 Dodecane
16 Tridecane
17 Tetradecane
18 Pentadecane
60M*0.53 mm column, N2 carrier
15M*0.25 mm column, H2 carrier
•
Increased sample throughput
•
Lower consumable cost
•
Improved separation
•
Increased sensitivity
