The Reaction of Normeperidine With an Impurity in Chloroform

When normeperidine is analyzed in a biological specimen and the extract is ultimately concentrated in chloroform, normeperidine reacts chemically to form an extraction artifact, normeperidine ethylcarbamate. This substance has a molecular weight of 305 and has gas chromatography indexes of 2206 and 2525 on OV-1 and OV-17, respectively. Normeperidine ethylcarbamate may be formed by the reaction of normeperidine and ethyl chloroformate, and evidence is presented to show that this same reaction produces the normeperidine artifact when this drug is boiled in chloroform in the process of solvent removal. Greater than 90% conversion of normeperidine to normeperidine ethylcarbamate occurred in some extraction procedures using chloroform. The implications of this reaction are considered with respect to analysis of normeperidine and other secondary amines.