A Closer Look at Acetyl and Pentafluoropropionyl Derivatives for Quantitative Analysis of Morphine and Codeine by Gas Chromatography/Mass Spectrometry

PFPA and acetic anhydride derivatives of morphine and codeine were evaluated with respect to stability, chromatography, potential for analytical interferences by other opiates, and suitability of major fragment ions for analysis by GC/MS with deuterated internal standards and selected ion monitoring (SIM). The PFPA derivatives showed acceptable stability and could be analyzed without interference from other opiates, but the codeine derivative had relatively poor chromatography and its mass spectrum had only two ions suitable for SIM. The acetic anhydride derivatives were stable and chromatographed well, but diacetyl hydromorphone enol, a minor product of derivatization of hydromorphone, interfered with analysis of morphine. 3-Monoacetylmorphine, a minor product of derivatization of morphine, prevented use of the abundant m/z 285 ion of derivatized D3-codeine as a qualifying ion in quantitative assays. The acetic anhydride derivative of morphine cannot be distinguished from the corresponding derivative of the heroin metabolite 6-monoacetylmorphine.