title: A liquid chromatography assay for the study of serum and gastric juice metronidazole concentrations in the treatment of Helicobacter pylori.
abstract: Metronidazole is an important component of combination antimicrobial therapies used in the eradication of Helicobacter pylori, a recognized cause of gastritis and duodenal ulcer. Studies are needed to understand which pharmacokinetic factors determine the success of metronidazole therapy and what role drug monitoring plays. Such studies require a rapid, accurate assay for small volumes of sample, including gastric juice, over a 200-fold range of concentrations. Using an isocratic high-performance liquid chromatography (HPLC) method, with an 8-min run time and protein precipitation of samples, metronidazole could be measured reliably to as low as 0.5 mg/L in 100 microliters samples of serum, gastric juice, or saliva. Standard curves for serum and gastric juice were linear between 0.5 and 50 mg/L. Within-day coefficients of variation (CVs) (n = 5 at six concentrations) ranged from 1.1 to 4.8% over this range and the between-day CV (n = 7 days) was 5.8%. Neither omeprazole nor common gastroenteric and cardiac medications interfered with this assay. A pilot study, done in four healthy volunteers given intravenous metronidazole 500 mg before and after 7 days of omeprazole therapy, found metronidazole to be present in higher concentrations in gastric juice and saliva than in serum 2 h after intravenous administration. The range and accuracy of the assay proved to be suitable for carrying out pharmacokinetic studies at clinically used doses of the drug.
authors.affiliation: Department of Medicine, Victoria General Hospital, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: P T
authors.initials: PT
authors.lastname: Pollak
mesh_terms: D000994:Antitrichomonal Agents / Q000032:analysis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004347:Drug Interactions; D005750:Gastric Juice / Q000737:chemistry*; D016481:Helicobacter Infections / Q000097:blood / Q000188:drug therapy; D016480:Helicobacter pylori; D006801:Humans; D008795:Metronidazole / Q000032:analysis* / Q000097:blood; D009853:Omeprazole / Q000737:chemistry
chemical_list: D000994:Antitrichomonal Agents; D008795:Metronidazole; D009853:Omeprazole