Hydromorphone metabolites: isolation and identification from pooled urine samples of a cancer patient

Abstract

1. Hydromorphone-3-glucuronide, dihydromorphine, dihydroisomorphine, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were isolated from a cancer patient's urine and identified as metabolites of hydromorphone by comparison with synthetic standards using LC/MS/MS with gradient elution. 2. The relative urinary recovery of dihydroisomorphine-3-glucuronide was estimated to be 17-fold higher than previously reported. 3. Three new metabolites, including hydromorphone-3-sulphate, norhydromorphone and nordihydroisomorphine, were tentatively identified.

Capillary electrophoresis contributions to the hydromorphone metabolism in man

“…The second, in particular, is similar to what was observed for HMOR (286 ? 185) and it is reported in the literature [9]. The simulation of this transition indicates that it could be due to the elimination of ring D (Fig.…”

“…1). In the literature, 6a-HMOROL is known under the name of dihydromorphine, while 6b-HMOROL is called dihydroisomorphine [9,12,13]. Accordingly, 6b-NHMOROL is reported as nordihydroisomorphine [9].…”

“…The enzymes involved in the 6-keto-reduction are not yet known. Among the phase II reactions, it is known that conjugation with glucuronic acid occurs with several HMOR metabolites [9,[12][13][14][15], and conjugation with sulfuric acid is reported to occur with HMOR [9]. The information regarding the metabolism of HMOR was gained from animal studies [12,13], via analysis of human body fluids, including urine [9,10,12], and in vitro incubations of HMOR with human liver microsomes or single enzymes [11].…”

“…1), a biotransformation that is catalyzed in vitro by the liver enzyme cytochrome P450 (CYP) system [9][10][11]. HMOR and NHMOR can be 6-ketoreduced to hydromorphol (HMOROL) and norhydromorphol (NHMOROL), respectively ( Fig.…”

“…For the analysis of HMOR and some of its metabolites in various biological matrices, methods based upon TLC [12], RIA [16,17], GC with flame-ionization [12], or MS [12,[18][19][20][21][22][23] detection, and HPLC with MS [9,10,18] or UV [24] detection have been developed. Furthermore, a HPLC-MS method was employed for the study of the HMOR metabolism in vitro via incubations with human liver microsomes and single enzymes [11].…”