Determination of 5-ASA in Whole or Partial Mesalamine Delayed-Release Tablets Recovered from Fecal Samples of Healthy Volunteers

Purpose: Mesalamine delayed-release tablets (Asacol®, Procter & Gamble Pharmaceuticals) have a coating of methacrylic acid polymer B (EUDRAGIT-S) that allows release of mesalamine to the proximal colon with low systemic absorption (approx. 28%). This coating is pH sensitive and is released at a sustained pH level above 7. Fragments of Asacol tablets have been observed in fecal specimens, but the fragments were believed to be shells left after the 5-ASA had been released. The current study was to determine the amount of 5-ASA in whole and partial mesalamine tablets recovered from the fecal samples of healthy volunteers who received mesalamine therapy. Methods: 30 healthy volunteers received two 400mg mesalamine tablets po bid for 4 days. After observing the presence of whole and partial mesalamine tablets in fecal specimens, the investigators recovered the tablets and fragments for further analysis. The tablets and fragments recovered from fecal specimens were photographed, crushed and added to 20mL 0.1M NaPO4 (pH 6.0) and 80mL absolute methanol. After resting at room temperature for 4 hours, 40mL of the solution was placed in a centrifuge for 10 minutes. Three 10mL aliquots of supernatant were removed, frozen and sent to a laboratory to be assayed for 5-ASA with a lower limit of quantification of 2000ng/mL. Results: Of 30 volunteers, 27(90%) provided fecal samples. Of these, 15 volunteers (55%) presented with at least 1 mesalamine tablet or fragment in at least 1 fecal sample. All tablets and fragments recovered had detectable 5-ASA. Mean recovery was 97.2 ± 47.1 mg per tablet/fragment-approximately 24% of an intact tablet. Conclusions: 55% of healthy volunteers who received oral mesalamine delayed-release tablets over 4 days of treatment excreted whole or partial tablets in at least 1 fecal specimen. Because all tablets and fragments recovered had detectable 5-ASA, the recovered tablets were not just physical matrices, inert shells or other excipients. Mean recovery was 97.2 ± 47.1 mg per tablet/fragment-approximately 24% of an intact mesalamine tablet. Only visually detectable fragments were measured in this study; additional undetectable fragments could have been present. The actual percentage of unreleased mesalamine may be higher than reported here and represents an important fraction of the daily mesalamine dose.