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

Although management of intractable pain usinglong-term intrathecal analgesic administration byimplantable infusion systems has become acceptableclinical practice, this method presentsunique challenges regarding the stability of thepharmaceutical agent(s) delivered. The stabilityand compatibility of a single drug such as hydromorphoneor bupivacaine, as well as mixturesof morphine-clonidine, have previously beenreported, but only using implantable infusion systemsand syringes under simulated clinical useconditions, not from implanted intrathecal pumps.The objective of this study was to assess thecompatibility and stability of drug mixtures fromintrathecal pumps placed in patients.For this case-series, 5 patients with intrathecalpumps who presented to the pain clinic for refillwere randomly selected. An aliquot of sampleextracted from the pump and an aliquot of newmedicine used for pump refill were collected. Highperformance liquid chromatography (HPLC) wasused to compare the 2 samples.Drug samples used were as follows: (A) hydromorphoneonly, (B) morphine and bupivacaine,(C) hydromorphone and ziconotide, (D)ziconotide and baclofen; and (E) hydromorphone,ziconotide, and baclofen. Samples B and E appearedto be stable when placed in situ in theSynchroMed II intrathecal pump based on theHPLC analysis. However, samples A, C, and Dappeared to have undergone some degradationand/or byproduct formation as noted in the graphicaldisplay 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 inthe intrathecal pump increases, or (b) when acombination of drugs is used in the intrathecalpump (as opposed to a single drug), some drugdegradation and/or byproduct formation happensas seen on HPLC.This is the first reported study assessing thecompatibility and stability of drug mixtures from intrathecalpumps. While the above reported HPLCdata reveals quantitative differences, furtherqualitative analysis is required for confirmationand possible identification of possible degradationand/or byproducts.Key words: Degradation, high performance liquidchromatography, intrathecal pump