Stability of sufentanil and baclofen mixtures for intrathecal analgesia at different concentrations in polypropylene syringes

Ann Pharm Fr. 2018 Nov;76(6):444-452. doi: 10.1016/j.pharma.2018.05.002. Epub 2018 Jun 23.

Abstract

Background: Intrathecal analgesia is a method using various molecules alone or in combination. Among these, the association sufentanil/ baclofen is widely used. Instead of moving patients to the few expert centers taking charge of these specific preparations, it could be better to transport syringes to peripheral centers managing pump refilling. That is why, it is interesting to demonstrate the stability of the mixture, and so to be able to ensure the best transport conditions of syringes.

Methods: A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Four mixtures of sufentanil baclofen stored in 5±3°C and 25±2°C were evaluated for seven days and compared to the initial observed concentrations.

Results: The stability is demonstrated only for preparations stored at 5±3°C for seven days thanks to relative concentrations (95% confidence intervals of the mean of 3 samples) systematically positioned between 90% and 110%. On the other hand, after few days, degradation products of sufentanil appeared for all mixtures stored at 25°C±2°C.

Conclusion: This study shows the stability of a weakly and a highly concentrated mixture of sufentanil and baclofen solutions in polypropylene syringes stored at 5±3°C for seven days. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.

Keywords: Baclofen; Baclofène; ICH; Méthode indicatrice de stabilité; Polypropylene syringe; Seringue polypropylène; Stability indicating method; Sufentanil; UPLC-DAD.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / analysis*
  • Analgesics, Opioid / therapeutic use
  • Baclofen / administration & dosage
  • Baclofen / analysis*
  • Baclofen / therapeutic use
  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Drug Storage
  • Injections, Spinal
  • Muscle Relaxants, Central / administration & dosage
  • Muscle Relaxants, Central / analysis*
  • Muscle Relaxants, Central / therapeutic use
  • Polypropylenes
  • Sufentanil / administration & dosage
  • Sufentanil / analysis*
  • Sufentanil / therapeutic use
  • Syringes

Substances

  • Analgesics, Opioid
  • Muscle Relaxants, Central
  • Polypropylenes
  • Sufentanil
  • Baclofen