New investigations into the stability of Mesna using LC-MS/MS and NMR

Expert Rev Anticancer Ther. 2016;16(1):123-30. doi: 10.1586/14737140.2016.1121106.

Abstract

Introduction: It is important for sarcoma patients to receive the correct dose of Mesna as an adjuvant with ifosfamide to reduce the risk of hemorrhagic cystitis. This paper describes a study conducted to evaluate the physicochemical stability of Mesna for injection formulation over 14 days.

Methods: Mesna samples (n = 4, 20 mg/ml) were incubated in glass vials at 37 + 0.5ºC. Mesna concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS), and nuclear magnetic resonance spectroscopy (NMR) was used to detect degradation products. Evaporative losses and pH were also monitored.

Results: Our results differed from those published in existing literature. Both LC-MS/MS and NMR indicated that Mesna was unstable. The mean percentage decrease in Mesna concentration was 40% by day 14 of the analysis. The presence of Mesna's dimer Dimesna was detected on day 0 and its concentration increased over time. Dimesna was the only by-product identified.

Conclusion: Both LC-MS/MS and NMR analyses confirmed the instability of Mesna and its conversion into Dimesna.

Keywords: Dimesna; Mesna; chemotherapy; sarcoma; stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Chromatography, Liquid / methods*
  • Drug Stability
  • Drug Storage
  • Hydrogen-Ion Concentration
  • Injections
  • Magnetic Resonance Spectroscopy / methods*
  • Mesna / analogs & derivatives
  • Mesna / analysis*
  • Mesna / chemistry
  • Tandem Mass Spectrometry / methods*

Substances

  • 2,2'-dithiodiethanesulfonic acid
  • Mesna