COTRIMOXAZOLE AND STAVUDINE INTERFERENCE IN A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS FOR DIDANOSINE IN HUMAN PLASMA

Recently, the authors were confronted with interference of stavudine a nd co-trimoxazole when analyzing the antiretroviral drug didanosine (d dI) in plasma of HIV-1-infected patients using reverse-phase high-perf ormance liquid chromatography with ultraviolet detection. After increa sing the percentage of methanol in the mobile phase from 4% to 8% vol/ vol and after decreasing the pH of the mobile phase from 6.8 to 5.8, t he authors were able to separate didanosine from stavudine and co-trim oxazole (both are frequently used drags in combination with didanosine ). Subsequently, the adapted bioanalytic methodology was validated, an d validation results showed that this new methodology can be used for the quantitative determination of didanosine in human plasma. This obs ervation makes clear that combination therapy for human immunodeficien cy virus with multiple (often chemically related) drugs has the potent ial of unexpectedly complicating bioanalytic analyses because therapeu tic strategies may change rapidly after publication of a bioanalytic m ethodology. Thus, it is evident that the investigation of interference of potentially coadministered drugs should be a standard procedure du ring the development of any bioanalytical methodology in any laborator y.