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Extract Preparation in Chemical Characterization Studies – Evaporation

Catalog of Regulatory Science Tools to Help Assess New Medical Devices 

The Evaporation tool provides a predictive model for estimation of the recovery of analytes in chemical characterization studies following concentration through rotary evaporation or nitrogen blowdown.

Technical Description

The RST is a model which estimates the impact of evaporation method parameters on recovery of extractables in chemical characterization studies. In the model, the recovery of an established universe of extractables from medical devices (chemicals) is calculated from the displacement of evaporated analyte with air.  This recovery is then compared through quantitative structure-property relationship equations to determine the solvent/air partition coefficients (K). The model’s input parameters are temperature, solvent vapor pressure, solvent molecular weight, solvent density, initial volume, partition coefficients (K), and final (evaporated) volume. A framework is also presented in the User Manual which provides instructions on how to select reference standards for evaluation of solvent evaporation and apply the model to a universe of chemicals. The model and framework for estimating recovery of a universe of chemicals is described in additional detail in a peer-reviewed publication ( Duelge, K.J., Young, J.A. Estimating Recovery in the Evaporation Chemical Space. Biomedical Materials & Devices 2, 1205–1214 (2024). https://doi.org/10.1007/s44174-024-00163-7). 

The model has been qualified for the following conditions:

  • Solvents – water, 0.9% saline, dichloromethane, hexanes, and isopropyl alcohol
    • Solvents evaluated represent a range of molecular weights (18 to 114 g/mol), densities (0.66 to 1.3 g/mL), and vapor pressures (0.16 to 0.47 atm at 20°C)
  • Temperature – 25° to 50°C
  • Extent of evaporation – 0-90% reduction from the initial solvent volume
  • Evaporation using a stream of nitrogen (nitrogen blowdown) and rotary evaporation

Using the input parameters and models described, the outputs are an estimation of the recovery of extractable chemicals. One can then examine the recovery for all compounds in the universe and obtain an estimate of total coverage based on the experimental parameters selected. 

Intended Purpose 

The RST allows the user to determine the impact of experimental parameter selection on recovery of extractables when solvent evaporation is used in a chemical characterization study and compare the impact of parameter selection across different laboratories.  This information can then be applied to the universe of extractables and predetermine their recovery behavior in an evaporation process, including using nitrogen blowdown and rotary evaporation methods.   The presented model applies to medical devices extracts (using the solvents indicated in this tool) which are generated as part of a chemical characterization study.  The model assists device manufacturers and test laboratories establish a broadly applicable rationale for selecting the most appropriate experimental conditions and reference standards based on their needs.

Testing

The model and framework described has been tested and qualified by demonstrating accurate prediction of recovery for a variety of extractables and a range of experimental parameters. These tests included a range of values for temperature, solvent vapor pressure, solvent molecular weight, solvent density, initial volume, and final (evaporated) volume for 11 analytes.  The analytes were chosen to demonstrate a range of Kd values to evaluate recovery from 0% to 100% under various conditions.  Each test was preformed in triplicate, with a total root mean square error of <20%.  The instructions provided in the User Manual incorporate a requirement for each laboratory intending to use the tool to demonstrate the model is effective for their internal processes by establishing the laboratory-specific recoveries empirically. The details of testing performed to verify the model and framework performance is described in detail in the publication as well as the supporting documents.

Limitations

The tool is limited to evaporation from water, 0.9% saline, dichloromethane, hexanes, and isopropyl alcohol; although these concepts can be applied to other solvents if verified using the same principles applied herein. The tool does not address other solvents or extract preparation methods such as liquid-liquid extraction or solid phase extraction. The tool has been evaluated specifically for evaporation under a stream of nitrogen (NE) and rotary evaporation (RE). Additionally, the tool is limited based on the applicability domain of the prediction models used. Specifically, inorganic solutes, most organometallic solutes, and any solutes which contained no carbon atoms were removed and excluded from the training set for predicting K.

Supporting Documentation

Peer-reviewed publication and supporting documentation (Duelge, K.J., Young, J.A. Estimating Recovery in the Evaporation Chemical Space. Biomedical Materials & Devices 2, 1205–1214 (2024). https://doi.org/10.1007/s44174-024-00163-7).

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