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74 <strong>principles</strong> <strong>of</strong> <strong>extraction</strong><br />

Extraction plate<br />

Collection plate<br />

Organic solvent: methyl ethyl ketone<br />

Diatomaceous earth particle<br />

Aqueous plasma layer<br />

Solid<br />

Support<br />

chlor<strong>of</strong>orm within 45 seconds when <strong>the</strong> flow was very slow or stopped, corresponding<br />

with molecular di¤usion time. The <strong>extraction</strong> system required no<br />

mechanical stirring, mixing, or shaking.<br />

Solid-supported LLE is a new approach reported by Peng et al. [49,50].<br />

They exploited <strong>the</strong> e‰ciency <strong>of</strong> 96-channel, programmable, robotic liquidh<strong>and</strong>ling<br />

workstation technology to automate methodology for this LLE<br />

variation. A LLE plate was prepared by adding inert diatomaceous earth<br />

particles to a 96-well plate with hydrophobic GF/C glass fiber bottom filters.<br />

Samples <strong>and</strong> solvents were added to <strong>the</strong> plate sequentially. LLE occurred in<br />

<strong>the</strong> interface between <strong>the</strong> two liquid phases <strong>and</strong> on <strong>the</strong> surface <strong>of</strong> individual<br />

particles in each well (Figure 2.18). The organic phase extracts were eluted<br />

under gentle vacuum into a 96-well collection plate. The approach was used<br />

for initial purification <strong>of</strong> combinatorial library samples <strong>and</strong> for quantitative<br />

analysis <strong>of</strong> carboxylic acid–based matrix metalloprotease inhibitor compounds<br />

in rat plasma.<br />

2.3. LIQUID–SOLID EXTRACTION<br />

When a liquid is extracted by a solid, phase A <strong>of</strong> <strong>the</strong> Nernst distribution law<br />

[equation (2.2)] refers to <strong>the</strong> liquid sample, <strong>and</strong> phase B, <strong>the</strong> extracting<br />

phase, represents <strong>the</strong> solid (or solid-supported liquid) phase:<br />

KD ¼ ½XŠ B<br />

½XŠ A<br />

Analyte<br />

Plasma<br />

Layer<br />

Analyte<br />

Organic<br />

Solvent<br />

Organic<br />

Solvent<br />

Figure 2.18. Schematic representation <strong>of</strong> automated liquid–liquid <strong>extraction</strong>. (Reprinted with<br />

permission from Ref. 50. Copyright 6 2001 American Chemical Society.)<br />

ð2:2Þ<br />

Classically, batch-mode liquid–solid <strong>extraction</strong>s (LSEs), were used to con-

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