Are fluorine-rich pharmaceuticals lost by partition into fluorous phases?

[Display omitted] •Potential partition of fluorine-rich drugs from solvents into fluorocarbons was measured by a high throughput LC–MS method.•No significant loss of fluorine-rich compounds into the fluorous phase from a wide range of organic solvents was observed.•Droplet microfluidics with fluorou...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2016-09, Vol.128, p.106-110
Main Authors: Sun, Shuwen, Zawatzky, Kerstin, Regalado, Erik L., Mangion, Ian K., Welch, Christopher J.
Format: Article
Language:English
Subjects:
Chromatography, Liquid - methods
Droplet microfluidics
Fluorine - chemistry
Fluorine-rich pharmaceuticals
Fluorocarbons - chemistry
Fluorous phase partition
Mass Spectrometry - methods
Microfluidic Analytical Techniques
Microfluidics - methods
Multiple injections in a single experimental run
Pharmaceutical Preparations - chemistry
Solvents - chemistry
Water - chemistry
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Summary:[Display omitted] •Potential partition of fluorine-rich drugs from solvents into fluorocarbons was measured by a high throughput LC–MS method.•No significant loss of fluorine-rich compounds into the fluorous phase from a wide range of organic solvents was observed.•Droplet microfluidics with fluorous carrier fluid can be used for organic reactions without causing compound loss. The recently developed technology of droplet microfluidics has demonstrated great potential for many applications such as biochemical assay, high throughput screening, cell culture, directed evolution, and chemical synthesis. Intrigued by its capabilities for miniaturization, flexible manipulation, rapid reagent mixing and high throughput experimentation and analysis, the pharmaceutical industry has begun to investigate droplet microfluidic implementation in medicinal and process chemistry. Segmented by an immiscible secondary phase, usually perfluorinated oil, aqueous or organic droplets serve as individual micro-reactors without suffering cross-contamination. As many drug molecules contain fluorines, it is necessary to investigate whether such compounds will be preferentially extracted into the fluorous phase via fluorophilic solvation, which could lead to erroneous analytical results. In this work, we chose drugs with up to 10 fluorines to probe their partition into perfluorodecalin (PFD) from a variety of organic solvents. A fast and straightforward MISER (Multiple Injections in a Single Experimental Run) LC–MS method was applied to measure the loss of drug after mixing with PFD. We found that no significant partition occurred, with the concentration of drugs in the ‘experimental’ group measured as ±10% of the ‘control’ group. The RSD% of multiple injections is
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2016.05.025