Validation of drug compounding for intrathecal analgesia

Background and objective

Currently, in clinical oncology practice, some patients remain painful despite the use of high dose of intravenous opioids. Intrathecal analgesia becomes the last solution to control acute pain. A program for the pain treatment by intrathecal analgesics has been set up in our hospital. In this context, the pharmacy department has to prepare and control administered analgesic drugs. The aim of this study is to develop an analytical method for quality control and to assess the stability of the drugs.

Setting and method

For intrathecal analgesic treatment, an admixture of 4 drugs may be used over a wide concentration range : morphine (0.625 – 10mg/mL), ropivacaine (0.625 – 10mg/mL), baclofen (0.0625 – 1mg/mL) and clonidine (1.25 – 20µg/mL). Therefore, we have validated an HPLC-UV method suitable for quality control of drug compounding as well as stability assessment. Five syringes have been assessed over 48 hours at 4°C at intermediate concentrations of morphine (2.5mg/mL), ropivacaine (2.5mg/mL), baclofen (0.25mg/mL) and clonidine (5µg/mL) in order to evaluate conditions for storing and transporting admixtures.

Results

The validation of chromatographic method has been demonstrated. Statistical bias obtained are less than 10.0% and coefficients of variation calculated during 5 days are below 5.0%. In a second time, stability in syringes has been checked by evolution of analgesic concentrations. The percentage obtained after 48 hours at 4°C was : 104.7% for morphine, 105.2% for ropivacaine, 103.6% for baclofen and 96.5% for clonidine. In the same order, pH and osmolarity remain stable. We can observe a variation of 1.2% for pH and 3.5% for osmolarity after 48 hours.

Conclusion

The accuracy and precision of the method have been established. At intermediate concentrations, we can conclude on the stability of these 4 molecules at 4°C in admixtures. All these results allow to store analgesia syringes over 48 hours after drug compounding.