Chemometric optimization of derivatization reactions prior to gas chromatography–mass spectrometry analysis

• Chemometric optimization of derivatization reactions prior to GC/MS analysis.
• Application as a model of 24 pharmaceuticals from six drug classes.
• The use of principal component analysis to optimize derivatization.
• The first application of cluster analysis in this context.
• Validation of SPE-GC/MS and its application to the analysis of drugs in real samples.

Derivatization is a methodological technique that can be used to make an organic compound more suitable for qualitative and/or quantitative analysis (e.g. pharmaceuticals). However, many analysts try to avoid this analytical procedure as it is time-consuming and labour-intensive. On the other hand, an inter-laboratory study demonstrated that with regard to sensitivity and measurement uncertainty, gas chromatography coupled to mass-spectrometry was superior to liquid chromatography coupled to mass spectrometry for the trace analysis of organic compounds in matrices of greater complexity. In our previous paper (Kumirska et al., J. Chemometr. 25 (2011) 636–643) we suggested using principal component analysis (PCA) to optimize the derivatization of six compounds (5 oestrogenic steroids and diethylstilbestrol) prior to GC–MS analysis. In the present work we applied a highly sophisticated model – 24 pharmaceuticals derived from six classes of drugs. The efficiency of different derivatization reactions was evaluated by PCA and compared with that obtained from cluster analysis (CA), the latter method being applied in this context for the first time. Derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine and ethyl acetate (2:1:1, v/v/v) for 30 min at 60 °C was found to be optimal. The SPE-GC–MS method was also validated and successfully applied to the analysis of selected pharmaceuticals in wastewater and surface waters in Poland.