Small Molecules

Bioanalysis of small molecules at TetraQ uses liquid chromatography-tandem mass spectrometry (LC-MS/MS). This technology combines high sensitivity with high selectivity for analyte quantitation in complex matrices such as plasma, serum, urine or tissue homogenates. Protein precipitation, liquid-liquid extraction or solid phase extraction (SPE) is used for initial sample work-up. Parent active and metabolite(s) may be analysed together in a single run, assuming the availability of suitably pure reference items. In favourable cases, multiple small molecule biomarkers or natural products can also be analysed in parallel.

TetraQ’s small-molecule capacity includes the following SCIEX instruments

We can also offer access to metabolite screening through the University of Queensland’s Centre for Clinical Research, using a TripleTOF 5600 system to identify potential metabolites of a parent active and provide estimates of relative abundance. This analysis is best carried out on clinical samples at varying dose levels and time points. Metabolite screening can be run after pharmacokinetic analysis of the same samples is complete.

In favourable cases, LC-MS/MS can be used to achieve a lower limit of quantitation below nanogram per millilitre levels. For best outcomes, TetraQ recommends that sponsors obtain an internal standard that is a stable isotope-labelled version of the analyte of interest, such as a deuterium- or carbon-13-labelled form of analyte. It is usually possible to obtain isotope-labelled internal standards from specialty suppliers. However, lead times may be several months for custom synthesis and purification. TetraQ is happy to advise sponsors on labelling of internal standard and the quantities of reference material and internal standard needed for method work and subsequent sample analysis.  

In cases where analytes are known to be unstable, TetraQ will work with sponsors  to identify conditions that will avoid loss of analyte during processing at the clinical site or in storage. We can carry out additional validation to test sample stabilization. We can also provide custom PK kits with stabilizing additives and laboratory manuals outlining suitable processing conditions. Contact us at for a more detailed discussion.