Gas Chromatography Method Development Case Studies

CASE STUDY 1

Method Development and Validation of a Capillary Gas Chromatography Method for the Determination of Aldehydes in Pharmaceutical  Excipients.

 Problem:

A client was using an HPLC method for the determination of aldehydes employing DNPH derivation. The testing was used to select appropriate excipients to reduce stability concerns. The method had problems with certain excipients. This resulted in possible quality issues and delays in lot approval.

 Solution:

Quantex developed a headspace gas chromatography (HS-GC) method, based on the derivatization of aldehydes in aqueous solution with PFBHA.

  • The method was developed and optimized to identify and quantify for low levels of C1-C8
  • The developed method overcame problems with the matrix .
  • The method was  then validated and  demonstrated to  be  linear, accurate, precise, specific and  
  • The method allows the  client to  quickly analyze excipients for  the  presence of aldehydes. 

CASE STUDY 2

Method Development and Validation of a Gas Chromatographic Method for the Determination of Impurities in Recovered Process Solvent.

 Problem:

A client was recovering an alcohol used in its manufacturing process. Rather than dispose of the recovered alcohol, the client purified it for re-use in its process. Other solvents used in the process in small amounts had to be monitored so that the recovered and purified alcohol was acceptable for reused. The GC method used by the client had problems in separating and quantifying the impurities.

 Solution:

Quantex determined that the method employed by the client needed to be modernized. Rather than use a packed column, as was done by the client, a capillary column would yield a superior separation. However, the available equipment at the client’s manufacturing location could not handle modern capillary columns. Quantex chose to develop a method that employed a megabore gas chromatographic column.

  • Quantex scientists determined that a suitable column was a Q-Plot type This would allow for the separation of both the aromatic hydrocarbon and ketone solvent impurities from the alcohol.
  • megabore capillary column was selected, since such a column could be installed into a gas chromatograph that was using packed GC
  • The method was developed and optimized for the separation and quantitation of the impurities, and the determination of alcohol
  • The method was then validated and demonstrated to be linear, accurate, precise, specific and robust of each impurity, and alcohol
  • The method was then successfully transferred to the client’s manufacturing

Case Study 3

Development of a Gas Chromatographic Method to Overcome Matrix interference with and HPLC Method.

 Problem:

An API manufacture was using an HPLC method to monitor and control the formation of phenolic impurities in this specific API. As a result of the process chemistry, from time to time, the method had problems with the matrix that affected the performance of the detector. This resulted in the inability to effectively monitor the process and caused problems in controlling impurity   formation.

 Solution:

In reviewing the process chemistry and the potential impurities of concern, Quantex scientists determined that a gas chromatographic method was a suitable solution. Initially, a screening method was developed employing GC-MS. The objective was to determine whether the problems with the HPLC method was an unknown impurity of just a problem with the process chemistry matrix. By screening samples that created problems with the HPLC detector, the analysis by GC-MS confirmed that it was an intermittent matrix issue. A capillary GC method was then developed employing GC-MS to monitor the chromatographic separation of the phenolic impurities without matrix interference. The method was then transferred for use employing GC-FID.

  • The method was developed and optimized employing GC-MS to identify and quantify for potential phenolic impurities.
  • The developed method overcame problems with the matrix .
  • The method was then transferred employing the use of Gas chromatograph with an FID (GC-FID).
  • The method was then validated and demonstrated to be linear, accurate, precise, specific and robust for the phenolic impurities of