Determination of Degradation Products of Cyclobenzaprine Hydrochloride, Lidocaine and Piroxicam in a Semi-Topical Formulation: MS-MS Confirmation of Unknown Impurities

J Chromatogr Sci. 2016 Jul;54(6):902-11. doi: 10.1093/chromsci/bmw009. Epub 2016 Apr 7.

Abstract

Association of cyclobenzaprine hydrochloride, piroxicam and lidocaine in a topical formulation is one of the newest innovations in the pharmaceutical formulary field. In this study, a reversed-phase liquid chromatographic method was developed for the establishment of the impurities of cyclobenzaprine hydrochloride, lidocaine and piroxicam in the semisolid topical formulation. In this study, we not only determined 2,6-dimethylaniline, 2-pyrydilamine but also specified impurities of cyclobenzaprine hydrochloride (dibenzosuberenone, amitriptyline, carbinole, cyclobenzaprine N-oxide and anthrachinone). The target compounds were determined using a mobile phase that consisted of a mixture of phosphate buffer (0.025 M; pH 6.2)-acetonitrile-methanol (60 : 13 : 27, v/v/v). A minimum of three supplementary possible degradation products were determined. Using mass spectrometry, the unspecified impurities were identified and the use of correlation matrices permitted the association with the possible source compounds. The chromatographic conditions were qualified and validated according to ICH guideline requirements to confirm specificity, linearity, accuracy and precision.

MeSH terms

  • Amitriptyline / analogs & derivatives*
  • Amitriptyline / analysis
  • Amitriptyline / chemistry
  • Lidocaine / analysis
  • Lidocaine / chemistry*
  • Piroxicam / analysis
  • Piroxicam / chemistry*
  • Tandem Mass Spectrometry*

Substances

  • Piroxicam
  • Amitriptyline
  • cyclobenzaprine
  • Lidocaine