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June 13, 2024 Dr Pramod Kr Pandey
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GC method adjustments USP way

Introduction and outcome

GC method adjustments are required during routine analysis of pharmaceuticals analysis. Analysis can not begin if the GC system fails in the system suitability test as per standard testing procedure (STP). Now the question is why does the GC system fail in the system-suitability test and what is its solution? This is a very critical situation for any analytical or QC professionals. That is why I decided to share my skill-based knowledge on this topic. In this article, I will discuss reasons for failing the system suitability-test, the need of adjustment in the GC method, necessary and sufficient conditions under which adjustments can be made in the GC method, case studies and frequently asked questions. This post will clear all your doubts related to GC method adjustment and your knowledge will increase to the next level.

Why does the GC system fail in the system suitability test?

The following factors may lead to failure in the system-suitability test and variation in the retention time (RTs), relative retention time (RRTs), co-elution of peak, and elution pattern:

  • Laboratory temperature: Due to variations in the laboratory temperature, solvent, diluent and sample may evaporate
  • Solvent quality: The purity of the solvent may affect the system suitability test
  • Column life: Column life is inversely proportional to the number of injections. The new column performs and pass the system suitability test easily whereas an old column needs adjustment in the GC conditions
  • Carrier gas purity: Impre carrier gas may lead to a lot of noise in the chromatogram and failure of the system-suitability test
  • Column brand: The same column of different brands may give different retention times for an analyte
  • Column dimension and stationary phase coating: SST may fail or RTs and RRTs may change while changing dimension or stationary phase particle size

Hence, GC condition needs adjustment to meet RTs, RRTs, SST criteria and elution pattern.

Need for GC method adjustments

When GC fails in RTs, RRTs, SST criteria and elution patterns, these failures require adjustment in the GC method . System-suitability test can also fail if equivalent columns are used. That is why the GC condition is adjusted to meet the RTs, RRTs, SST criteria and elution patterns.

Necessary and sufficient conditions for GC method method adjustments

  • SST criteria must be within the acceptance limit
  • There must be the same elution pattern as in the monograph method
  • All impurities must be detected and pass the acceptance criteria
  • All impurities must fulfil sensitivity or quantitation limit acceptance criteria and
  • Must pass in linearity and resolution test

GC method adjustments

Adjustments in GC capillary column
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Particle size (For packed column) adjustment

Maximum allowable reduction of particle size is 50%. No increase in particle size is allowed.

Note: Now a days packed columns are not used due to its low efficiency.

Film thickness adjustment (for capillary columns) adjustment

Allowable adjustment in the film thickness is -50% to 100%.

Example: If the film thickness of the USP monograph method is 0.50µm then allowable adjustment will be 0.25µ m to 0.75 µm

Column length adjustment

Allowable adjustment in the Column length is -70% to 100%.

Example: If the column length of the USP monograph method is 50 meter then allowable adjustment will be 35 m to 75 m

Column Internal diameter adjustment

Allowable adjustment in the Column diameter is ± 50%

Example: If the column internal diameter of the USP monograph method is 300 µm then allowable adjustment will be150µm to 450µm

Column temperature adjustment

Allowable adjustment in the Column temperature is ± 10oC

Adjustment in the column-oven temperature program

Allowable adjustment of ramp rate and hold time is permitted upto ±20%

Flow rate of the carrier-gas adjustment

Adjustment of the flow rate by ±50% is permitted.

Example: If the flow rate in any method is 10 mL/minute. Then it will be adjusted between 5 mL/minute to 15 mL/minute

Injection volume and split ratio adjustment

  • SST criteria must be within the acceptance limit
  • All impurities must be detected and full-fill sensitivity/QL acceptance limit
  • Must pass in linearity and resolution test

Adjustment in injection volume and split ratio adjustment can be made to meet the SST requirement. But the modified injection volume must pass the following parameters:

Adjustment in injection port temperature and transfer-line temperature in static headspace conditions

Allowable adjustment in injection port temperature and transfer-line temperature ± 10oC, provided no decomposition or condensation occurs

Conclusion

This USP guideline on adjustment in the GC chromatographic method is very helpful for both quality control and analytical professionals. For In-house or method of other sources revalidation or mini validation must be performed and mini-validation must include all allowable changes. Now I hope all your doubts have cleared related to this topic and you can apply it more effectively during GC method development and routine analysis.

FAQs

Why some time GC fails in system suitability test?

System suitability test may fail due to improper column conditioning, column degradation, purity of the carrier gas, lab temperature and purity of the solvents

What are the allowable change in GC condition?

Allowable adjustment in the column length is -70% to 100%, film thickness is -50% to 100%, and flow rate is ±50%.

How much change is allowed in the GC method without revalidation? What are the allowable adjustment for USP?

Allowable adjustment in the column length is -70% to 100%, film thickness is -50% to 100%, and flow rate is ±50%.

Can these adjustments be allowed in all GC methods?

It will be applied to all GC monograph methods of USP. It can not be applied in-house or other methods. Keep in mind any adjustment must pass the system suitability test.

Can above adjustment be applicable to all USP monograph?

Yes. Keep in mind changes must pass the system suitability test

Abbreviations

  • QC: Quality control
  • RT- Retention time
  • RRT: Relative retention time
  • USP: United States pharmacopeia
  • SST: System suitability test
  • µm: micrometer

References

  • USP General chapter <621>
  • Instrumental method of analysis; Willard, Merritt, Dean and Settle

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