Determination of MPTP, a toxic impurity of pethidine

J Pharm Biomed Anal. 2003 Sep 15;33(1):1-6. doi: 10.1016/s0731-7085(03)00256-5.


Pethidine, predominantly a mu-receptor agonist, is a phenyl-piperidinic synthetic drug. It is used in the management of moderate to several pain. A possible hydrolytic degradation of an ester group can generate a very toxic compound, the N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) which contaminates the drug. Because of the toxicity of MPTP a suitable method for its determination must be selective and sensitive. Afterwards we propose simple methods to determine pethidine and MPTP by capillary electrophoresis (CE), MECK and RP-high performance liquid chromatography (HPLC) looking at the limit of detection obtained using these three techniques. CE was carried out using as running buffer ammonium acetate (pH 8.3). MECK was performed with a borate buffer (pH 8.3) containing sodium dodecylsulphate and trimethyl-beta-cyclodextrins. RP-HPLC was carried out on a RP18 stationary phase, using as mobile phase a mixture of phosphate buffer (pH 7) containing acetonitrile and 1% of diethylamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / analysis*
  • Analgesics, Opioid / analysis*
  • Chromatography, High Pressure Liquid
  • Chromatography, Micellar Electrokinetic Capillary
  • Drug Contamination
  • Electrophoresis, Capillary
  • Indicators and Reagents
  • Meperidine / analysis*
  • Reference Standards


  • Analgesics, Opioid
  • Indicators and Reagents
  • Meperidine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine