Identification of the acid-induced degradation products of omeprazole and 5-hydroxyomeprazole by high-resolution mass spectrometry.

RATIONALE: Omeprazole is used to treat gastric disorders and is one of the most commonly consumed drugs in the western world. It forms several metabolites but is mostly excreted unchanged and as 5-hydroxyomeprazole. Since omeprazole is widely prescribed, its excretion from the body has a potential environmental effect. After excretion it will enter the wastewater system and if not adequately removed during wastewater treatment will be discharged into rivers in the wastewater effluent. It is important to consider not only the parent drug, but also the main metabolite (5-hydroxyomeprazole) and their degradation products to fully understand the fate of this drug during wastewater treatment. In order to do this potential degradation products need to be determined. METHODS: Acid was used to artificially accelerate the degradation of omeprazole and 5-hydroxyomeprazole. A Q-Exactive Orbitrap mass spectrometer with an electrospray ionisation source was used to determine precursor and product ion data for the degradation products. RESULTS: Both starting materials quickly degrade under acidic conditions and the main degradation product formed in each case was a re-arranged monomer. Other species identified were doubly and singly charged dimers with varying numbers of sulphur atoms in the dimer bridge. Careful inspection of the accurate mass, isotope pattern, isotope abundance and product ion spectra was used to interpret the data. CONCLUSIONS: The resultant degradants from omeprazole and 5-hydroxyomeprazole were analogous to each other, differing only by an oxygen atom. This investigation determined the degradation products of omeprazole and 5-hydroxyomeprazole and proposed structures based on the accurate mass and isotope information. The product ions from the degradation products are also reported.

Prolonged ethanol administration prevents the development of tolerance to morphine-induced respiratory depression.

BACKGROUND: Opioid users regularly consume other drugs such as alcohol (ethanol). Acute administration of ethanol can rapidly reverse tolerance to morphine-induced respiratory depression. However, alcohol consumption by opioid users is likely to occur over prolonged time periods. We have therefore sought to determine the effect of prolonged alcohol consumption on the development of tolerance to opioid respiratory depression. METHODS: Mice were fed control or ethanol (5%) liquid diet for 16 days. On days 9-16 morphine tolerance was induced by administration of 3 priming injections of morphine followed by subcutaneous implantation of a morphine-filled osmotic mini-pump. Control mice received saline. Respiration was measured by plethysmography and the effect of an acute morphine challenge dose was measured on day 16 to assess the development of morphine tolerance. RESULTS: Prolonged ethanol consumption for 14 days did not alter the respiratory depressant effect of an acute dose of morphine. Control mice treated with prolonged morphine developed tolerance to acute morphine respiratory depression whereas ethanol diet fed mice treated with prolonged morphine showed significant respiratory depression during morphine-pump treatment and remained sensitive to the respiratory depressant effect of the acute challenge dose of morphine. The ethanol consumption did not alter blood or brain levels of morphine, whilst conversely prolonged morphine treatment did not alter blood levels of ethanol. CONCLUSIONS: Prolonged ethanol consumption prevents the development and maintenance of tolerance to the respiratory depressant effect of morphine. These data suggest that ethanol inhibition of tolerance will greatly increase the risk of fatal heroin overdose in humans.

Mapping health on the internet: a new tool for environmental justice and public health research.

This paper examines the prospects for integrating Internet platform GIS or 'web-GIS' into environmental justice and related public health research. Specifically, we document the development of a web-GIS created for investigating relationships between health, air quality and socioeconomic factors in Hamilton, Canada. After development of the web-GIS site, we assembled a focus group of public health professionals to test functionality and render opinions about the potential of the site and geographic information in their program implementation. Results show overwhelming support for the further integration of GIS into public health practice. The results also underscore the potential of web-GIS to alleviate concerns of cost and data availability that often limit the use of GIS in community debates centred on environmental justice issues.

Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths.