Prevalence of dihydrocodeine in hydrocodone positive postmortem specimens.

Hydrocodone (HC) has received renewed interest in the US due to reported increases in opiate related deaths involving psychotherapeutic drugs. The relative contribution of dihydrocodeine (DHC) in these deaths is unknown since little testing of this compound is performed. The objective of the study was to determine the prevalence of DHC in HC positive decedents and report the range of concentrations detected in these cases in order to evaluate the potential role of DHC in the deaths and determine the usefulness of including this analyte in opioid testing protocols. Specimens were assayed by liquid-liquid or solid phase extraction followed by gas chromatography/mass spectrometry operated in the selected ion monitoring mode. A multipoint calibration was utilized in the linear range 2-600ng/mL. Accuracy for HC, DHC and hydromorphone (HM) was 101-106% and between day precision at 160ng/mL between 7% and 11%. One hundred and thirty six cases were identified with the majority male (62%) and white (83%). A search of HC positive cases identified 64 with DHC (47%). The range of HC concentrations was 9-3039ng/mL heart blood (n=43) and 42-12353ng/mL urine (n=21). DHC concentrations in these cases ranged 3-243ng/mL in heart blood and 5-1842ng/mL in urine. DHC/HC ratios ranged 0.00(7)-2.90 in blood (n=43), and 0.01-5.04 in urine (n=21) with 16% and 24% of these cases with ratios >0.50, respectively. HM was detected in only 9 HC cases with the majority positive in urine.

Measurement of 10,11-dihydro-10-hydroxy-carbamazepine in serum and plasma by high-performance liquid chromatography.

BACKGROUND: Oxcarbazepine is an antiepileptic drug (AED) used to treat partial seizures as a monotherapy or adjunctive therapy. Oxcarbazepine is metabolized in the liver to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine (MHD). Optimal therapeutic effect and minimal toxicity can be achieved through monitoring MHD. METHODS: Serum/plasma was mixed with internal standard (5-ethyl-5-p-tolylbarbituric acid) in methanol and centrifuged for 10 min. The mobile phase consisted of phosphate buffer and acetonitrile (466:168 v/v). The supernatant was analyzed by liquid chromatography (LC) with UV detection at 210 nm. RESULTS: The linearity ranged from 1.0 to 50.0 microg/mL with analytical recovery of 101.3%-110.8%. The limit of quantification was 1.0 microg/mL. The intra-assay coefficient of variation (CV) was 7.0% and 2.0% for serum samples spiked at 16.3 and 35.8 microg/mL, respectively. The inter-assay CV was 4.3% and 2.3% for serum controls at 7.2 and 23.8 microg/mL, respectively. The method was correlated with a commercial LC-mass spectrometry method using 41 leftover patient samples containing MHD at concentrations of 1.0-36.4 microg/mL, showing a slope of 1.09, an intercept of 1.2 and r=0.9520. No interference was observed from commonly administered AEDs. Commercial controls containing more than 100 therapeutic drugs and endogenous substances were also tested and showed no interference. CONCLUSIONS: This method is simple and effective for monitoring MHD in serum/plasma.