METHOD: The effects of organic modifiers in mobile phase, protein precipitation agent to plasma sample ratio, and light on montelukast stability in unprocessed and processed human plasma, were evaluated. Validation was conducted in accordance with European Medicines Agency Guideline on bioanalytical method validation.
RESULTS: No interference peak was observed when acetonitrile was used as an organic modifier. Acetonitrile to plasma ratio of 4:1 produced clean plasma sample. Approximately 3 % of cis isomer was detected in unprocessed plasma samples while 21 % of cis isomer was detected in processed plasma samples after exposing to fluorescent light for 24h. The standard calibration curve was linear over 3.00-1200.00 ng/mL. All method validation parameters were within the acceptance criteria.
CONCLUSION: The validated method was successfully applied to a bioequivalence study of two montelukast formulations involving 24 healthy Malaysian volunteers. The light stability of a light sensitive drug in unprocessed and processed human plasma samples should be studied prior to pharmacokinetic/bioequivalence studies. Measures could then be taken to protect the analyte in human plasma from light degradation.
Methods: In a prospective study, colonoscopy was performed on 2,469 consecutive patients. Biopsies were taken from the terminal ileum and ascending, transverse, descending and sigmoid colon in all patients.
Results: Sixty-four of the 2,469 patients (2.6%) had eosinophilic gastroenteritis. Only five of the 64 patients (7.8%) with eosinophilic gastroenteritis had endoscopic mucosal abnormalities during colonoscopy. Six of these 64 patients (9.4%) had severe disease at presentation, and seven of these 64 patients (10.9%) required systemic steroid treatment. An elevated absolute peripheral eosinophil count was independently associated with severe disease at presentation (4/6 [66.7%] vs 3/58 [5.2%], p=0.005; odds ratio [OR], 25.320; 95% confidence interval [CI], 2.628 to 243.910), and severe disease at the time of presentation was independently associated with the use of systemic steroid treatment (6/7 [85.7%] vs 0/57 [0%], p=0.008; OR, 18.021; 95% CI, 2.163 to 150.152).
Conclusions: The prevalence of eosinophilic gastroenteritis is common, and patients usually present normal-appearing mucosa on colonoscopy. Those with severe disease at presentation usually have a raised absolute peripheral eosinophil count and should be commenced on systemic steroids as an initial therapy.