Validation Study of UPLC Method for Determination of Morphine, Ropivacaïne and Ziconotide in Combination for Intrathecal Analgesia

Abstract

Pain is often considered as the most feared symptom amongst individuals living with cancer. It can arrive at any stage during the course of the illness. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Use of analgesic admixture has been recommended by the most recent consensus conferences. Several studies found evidence of synergistic effects of intrathecal analgesic admixtures, most notably these containing ziconotide, morphine and ropivacaine, administering by a fully implantable pumps. The refills were prepared under a laminar airflow hood under strictly aseptic conditions, by the hospital pharmacist. This group of drugs that commonly used can be at the origin of errors inducing adverse effects in patients. In order to evaluate the accuracy of compounding of intrathecal admixtures, a new analytical method by simple liquid chromatography ultraviolet spectrometry method was developed and validated for the simultaneous quantification of three analgesic drugs (morphine, ropivacaine and ziconotide). The method was validated according to the recommendation of the US Food and Drug Administration (FDA). The method was linear, between 0.1 to 4 μg/ml for ziconotide, 0.1 to 10 mg/ ml for ropivacaine and 0.1 to 32 mg/ml for morphine. Forced degradation of ziconotide by acidic conditions allowed formation and detection of degradation products by the analytical method. This method can be considered as a stability indicating method. It is also part of a continuing quality process designed to improve accuracy of preparation.