Oripavine as a new marker of opiate product use

Abstract

During our extensive surveillance of opiates in urine specimens of opium users, we noticed the appearance of an unknown peak (compound X) in total ion chromatograms obtained by gas chromatography-mass spectrometry (GC-MS) after enzymatic hydrolysis and trimethylsilyl (TMS) derivatization. We identified the compound X as oripavine. Oripavine was found to be a new and useful putative marker of opium/poppy seed use in differentiation from heroin, pharmaceutical codeine, and pharmaceutical morphine use. The presence of oripavine in the urine of opium users is probably the result of O-demethylation of the opium alkaloid thebaine. Analytical method optimization for GC-MS detection of oripavine in urine was also undertaken. Underivatized oripavine could not be detected by GC-MS, and trials for derivatization of oripavine with acetic anhydride and propionic anhydride were unsuccessful. Trials were successful with bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane. It was also disclosed that almost all amounts of oripavine in human urine existed in the unconjugated form; it was absolutely necessary to hydrolyze the conjugate before TMS derivatization of oripavine for its GC-MS analysis.Keywords Oripavine Á Marker of opiate product use Á Opium Á Poppy seed Á Thebaine metabolism Á GC-MS

Confirmation of recent heroin abuse: Accepting the challenge

“…A further putative marker of opium/poppy seed use in differentiation from heroin, codeine, or morphine use is represented by oripavine, a presumptive O ‐demethylation product of the opium alkaloid thebaine . Although thebaine is an usual co‐extractant with morphine from opium, it is not an ingredient of illicit heroin because thebaine is degraded under the acetylation conditions used for street heroin synthesis.…”

“…Reticuline, a potential marker to differentiate opium use from the use of street heroin, poppy seeds, and codeine, respectively, was intro- A further putative marker of opium/poppy seed use in differentiation from heroin, codeine, or morphine use is represented by oripavine, a presumptive O-demethylation product of the opium alkaloid thebaine. 190 Although thebaine is an usual co-extractant with morphine from opium, it is not an ingredient of illicit heroin because thebaine is degraded under the acetylation conditions used for street heroin synthesis. Thus, neither thebaine nor oripavine detection is to be expected to result from illicit heroin administration.…”

Recent Advances in the Chemistry of Oripavine and Its Derivatives

“…The urine sample was subjected to enzymatic hydrolysis and derivatization for its GC-MS analysis. El Haj et al [38] proposed oripavine as a useful putative marker of opium use. They explained the presence of oripavine in the urine of opium users by the O-demethylation of thebaine.…”

“…Oripavine was converted to dihydroorvinone and its phenolic hydroxyl was protected with ethoxycarbonyl group (38). Grignard reaction with tert.-butylmagnesium chloride afforded the N-methyl-tertiary alcohol derivative (39).…”

Development of chromatographic methods for thebaine detection and quantification along with some of related alkaloid derivatives

“…There are also other methods described in the literature, such as oxidative colorimetric analysis [22], determination of opiates by circular dichroism [23], colorimetric determination [24], TLC analysis of opiate alkaloids and drugs [25,26], ELISA (enzyme-linked immunosorbent assay) analysis of thebaine [27], FTIR spectroscopy of opiates and chemometric analysis [28], differential pulse polarography [29] and even a voltammetric analysis of thebaine [30]. (6) and noscapine (7) T a b l e 2 [31], gas chromatography-ion trap mass spectrometry (GC-MS) analysis [32], liquid chromatographicatmospheric pressure chemical ionization mass spectrometric analysis [33] or HPLC analysis [34,35], GC-MS analysis [36][37][38][39]. Alkaloids are also being analyzed in environmental studies to trace the pollution of the environment [40].…”