STABILITY OF RIFAMPIN IN PLASMA - CONSEQUENCES FOR THERAPEUTIC MONITORING AND PHARMACOKINETIC STUDIES

Interest in determining plasma levels of rifampin for adjustment of do sage regimens has increased, but conflicting results exist concerning rifampin stability. The authors developed a high-performance liquid ch romatography assay to monitor rifampin plasma concentrations that was used to study the possible degradation of rifampin in plasma samples. This report describes the stability of rifampin in plasma kept at an a mbient temperature for 24 hours or stored at -20 degrees C for 2 weeks . The possible protective effect of adding ascorbic acid was also stud ied. The results indicate that rifampin degrades rapidly in plasma at an ambient temperature, and a 54% loss was observed within 8 hours. Th is degradation can be effectively prevented by adding ascorbic acid, t hus prolonging stability for up to 12 hours. The same results were obs erved with samples obtained as part of routine drug monitoring. Degrad ation was found to be greater at low rifampin concentrations. The auth ors subsequently demonstrated that decomposition of rifampin occurs af ter storage for 1 week at -20 degrees C. However, in samples supplemen ted with ascorbic acid before freezing, no degradation was observed wi thin 14 days at the two concentrations tested. Rifampin was more stabl e in specimens drawn from treated patients, suggesting possible in viv o stabilization of the molecule. Further studies are needed to determi ne stability of rifampin for longer storage periods. On the basis of t hese results, plasma samples obtained from patients receiving rifampin should be immediately supplemented with ascorbic acid and analyzed as soon as possible.