Physicochemical Profiling Services

Solubility Services


The extent to which a compound dissolves within a solvent is a physicochemical property measurement relevant across a wide range of industries.

Cyprotex focusses on solubility measurements within biologically-relevant aqueous media, in particular, those aligned to drug discovery.

For orally dosed drugs, poor solubility can limit its absorption from the gastrointestinal tract which can reduce oral bioavailability. Therefore, front-loading drug discovery campaigns with in vitro solubility measurements can mitigate against late-stage attrition due to DMPK factors.

Cyprotex has developed three distinct aqueous solubility assay-variants that align to differing needs:

  • High-throughput solubility mass spectroscopy (HT-Sol MS) method.
  • High-throughput solubility ultra violet (HT-Sol UV) method.
  • Turbidimetric solubility.


Solubility Services


What factors do I need to consider when measuring solubility?

An aqueous solubility measurement is relatively straight-forward to conduct but there are many compound-specific factors (e.g., crystalline or pre-dissolved in co-solvent initial form) and assay-specific factors (e.g., temperature, incubation time, buffer, separation technique, detection technique) to consider that can lead to experimental bias across these different permutations.1 Many approaches have been reported in the scientific literature driven in part by differing operational needs that effect the relevance of a measurement, e.g., the need to use DMSO stocks rather than solid material, the need for high-throughput automation, the use of shortened incubation times to facilitate more rapid turnaround of data.2

Please provide a further overview of the assays

We offer a turbidimetric method that is intended as a pre-screen solubility assessment. It runs at 37°C, to reflect the temperature of other in vitro DMPK assays, over a short incubation time using a pre-dissolved DMSO form of a compound. The solubilities measured are likely to be associated with a supersaturated systems and significantly higher than those of a more thermodynamically stable form .

Our high-throughput solubility mass spectroscopy (HT-Sol MS) and high-throughput solubility ultra-violet (HT-Sol UV) methods are intended to measure the aqueous media solubility associated with a more thermodynamically stable form of a compound using an incubation time of 24 hours. By employing a calibrated UPLC-MS/MS endpoint along with varying buffer dilutions, the HT-Sol MS dynamic range, in theory, can cover six orders of magnitude (e.g. ranging from 1 ng/mL to 1 mg/mL) providing that the compound’s MS response is suitable. By employing a UPLC-UV endpoint, the HT-Sol UV dynamic range is narrower at three orders of magnitude (e.g. ranging from 1 µg/mL to 0.125 mg/mL) but enables the provision of qualitative degradant information that can be supplemented with MS information where possible. From a drug discovery perspective, these two assays provide more pertinent measurements as the solubility associated to the more thermodynamically stable form of a compound should reflect the worst-case scenario in relation to modelling in vivo PK and early dose predictions.


1) Wenlock MC, Butler P. (2021) Drug solubility assessment. In: Talevi A (ed). The ADME Encyclopedia. Springer, Cham.
2) Könczöl A, Dargó G. Brief overview of solubility methods: recent trends in equilibrium solubility measurement and predictive models. Drug Discov. Today Technol. 2018, 27, 3–10.


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