A liquid chromatography method for quantifying caffeine dissolution from pharmaceutical formulations into colloidal, fat-rich media

Hywel D. Williams, David A Barrett, Robert W Ward, Ian J Hardy, Colin D Melia

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A simple and rapid high-performance liquid-chromatography method is presented that permits quantification of caffeine in colloidal fat emulsions proposed as new 'biorelevant' dissolution media (Intralipid™ and various milks). Using a mobile phase of 0.1 M sodium acetate (pH 4.0) and acetonitrile (89.5:10.5, v/v) at 1 ml min-1, the drug and internal standard (7-β-hydroxyethyltheophylline) were eluted within 8 min. Caffeine extraction was undertaken by protein precipitation in ice-cold 12% (w/v) trichloroacetic acid and centrifugation at 10,000 rpm for 15 min. This simple extraction method generated caffeine recovery values (corrected for % fat content) of 75.4 ± 1.4-100.6 ± 5.5%. The limit of detection was within the range 0.25-0.4 μg ml-1 and linearity was demonstrated in each medium up to 125 μg ml-1. Precision was <11.5% RSD and intra- and inter-day accuracy was 93.4-109.3%. The validated method was applied to in vitro USP dissolution tests in milk which compared the kinetics of caffeine release from (i) extended release matrices containing hydroxypropyl methylcellulose (HPMC) and (ii) an immediate release commercial analgesic tablet. Good reproducibility was obtained in both extended and immediate release dissolution tests. The method provides high-throughput quantification of this common drug in fat emulsions used as biorelevant dissolution media.

Original languageEnglish
Pages (from-to)1739-1745
Number of pages7
JournalJournal of Chromatography B
Issue number21
Publication statusPublished - 1 Jul 2010
Externally publishedYes


  • Caffeine
  • Fat emulsions
  • HPLC
  • HPMC matrices
  • Intralipid
  • Milk

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