MONITORING SULFASALAZINE THERAPY IN PATIENTS WITH CHRONIC INFLAMMATORY BOWEL DISEASE
Date
1980
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Sulfasalazine consists of sulfapyridine and 5-aminosalicylic acid moieties linked by an azo bond. It is used in the treatment of active inflammatory bowel disease and is the most effective agent for maintain-ing remission in chronic inflammatory bowel disease. A study conducted by Das and co-workers (Das et al, 1973b) indicated the therapeutic efficacy of sulfasalazine was related to serum concentrations of total sulfapyridine metabolites above 20 pg/ml. This investigation was ex-panded to study the relationship between adverse effects associated with sulfasalazine therapy and serum levels of sulfapyridine metabolites in a larger number (133) of patients (Das et al, 1973c). The occurrence of toxicity appeared to be related to serum conentrations of total sulfa-pyridine metabolites above 50 pg/ml. This and subsequent studies have shown an increased incidence of toxicity among patients who are slow acetylators of the sulfapyridine moiety.
To obtain more information about the relationships between serum concentrations of sulfapyridine metabolites, acetylator phenotype, and efficacy and toxicity of sulfasalazine therapy, a sensitive analytical procedure was needed. Therefore, a rapid, specific and sensitive high pressure liquid chromatographic procedure was developed for determination of sulfapyridine (SP) and its major metabolite, N4 -acetylsulfapyridine (AcSP), in biological fluids. Calibration curves were linear and the mean recovery of SP (AcSP) from serum, saliva and urine was 91.5 (82.0), iv88.6 (72.6) and 98.6 (90.6) %, respectively. A sensitive and specific gas chromatographic procedure for determination of SP and AcSP was also developed. However, this procedure was cumbersome in comparison with the high pressure liquid chromatographic procedure and was not used for monitoring sulfasalazine metabolites in the clinical study. The traditional spectrophotometric assay lacked specificity and did not provide adequate sensitivity for determination of sulfasalazine metabolites in small volumes of biological fluids.
Description
Keywords
inflammatory bowel disease, sulfapyridine
Citation
Degree
Master of Science (M.Sc.)
Department
Pharmacy