Stability and Compatibility of Drug Mixtures from Intrathecal Pump Using High Performance Liquid Chromatography

Abstract

Although management of intractable pain using long-term intrathecal analgesic administration by implantable infusion systems has become acceptable clinical practice, this method presents unique challenges regarding the stability of the pharmaceutical agent(s) delivered. The stability and compatibility of a single drug such as hydromorphone or bupivacaine, as well as mixtures of morphine-clonidine, have previously been reported, but only using implantable infusion systems and syringes under simulated clinical use conditions, not from implanted intrathecal pumps. The objective of this study was to assess the compatibility and stability of drug mixtures from intrathecal pumps placed in patients. For this case-series, 5 patients with intrathecal pumps who presented to the pain clinic for refill were randomly selected. An aliquot of sample extracted from the pump and an aliquot of new medicine used for pump refill were collected. High performance liquid chromatography (HPLC) was used to compare the 2 samples. Drug samples used were as follows: (A) hydromorphone only, (B) morphine and bupivacaine, (C) hydromorphone and ziconotide, (D) ziconotide and baclofen; and (E) hydromorphone, ziconotide, and baclofen. Samples B and E appeared to be stable when placed in situ in the SynchroMed II intrathecal pump based on the HPLC analysis. However, samples A, C, and D appeared to have undergone some degradation and/or byproduct formation as noted in the graphical display on HPLC. While sample A was a single-drug combination, the sample was in the pump for over 3 months; likewise, sample E was a 3-drug combination, however it was in the pump for only 30 days. Based on these results, it appears as though (a) when the length of time the drug stays in the intrathecal pump increases, or (b) when a combination of drugs is used in the intrathecal pump (as opposed to a single drug), some drug degradation and/or byproduct formation happens as seen on HPLC. This is the first reported study assessing the compatibility and stability of drug mixtures from intrathecal pumps. While the above reported HPLC data reveals quantitative differences, further qualitative analysis is required for confirmation and possible identification of possible degradation and/or byproducts. Key words: Degradation, high performance liquid chromatography, intrathecal pump