STABILITY AND COMPATIBILITY OF INTRATHECAL ADMIXTURES CONTAINING BACLOFEN AND HIGH-CONCENTRATIONS OF MORPHINE

We have found that the simultaneous intrathecal infusion of low concen trations of baclofen and morphine are of significant benefit in the tr eatment of both severe pain and spasticity. To extend the range of dru g concentrations for clinical use, the stability and physical compatib ility of baclofen and morphine sulphate admixtures containing high con centrations of baclofen and morphine sulphate have been examined. The studies reported demonstrate that baclofen and morphine in the admixtu res examined were stable for at least 30 days when stored at 37 degree s C. 4-(4-chlorophenyl)-2-pyrrolidone, a degradation product of baclof en was detected in all admixtures examined. Its concentration remained less than 1% of that of baclofen throughout the period of storage. Mo rphine-N-oxide, a potential degradation product of morphine, could not be detected in any of the admixtures examined. While the use of a hig hly sensitive and selective liquid chromatographic technique with on-l ine fluorescence detection revealed the presence of pseudomorphine and its time-dependent increase on storage, its concentration also consti tuted less than 1% of the parent drug. (C) 1997 Elsevier Science B.V.