To determine the potential clinical utility of peripheral opioid action using a clinical model of cancer treatment-induced inflammation and pain that allowed for topical application of morphine in the damaged tissue (oral mucosa). This pilot study followed a two blocks design. Ten patients with painful oral mucositis were enrolled in the first block (dose-response relationship finding) and randomized in two groups to receive oral rinses with 15 ml of either 1 per thousand or 2 per thousand morphine solution. Twenty-two patients were enrolled into the second block (efficacy and safety determination). Additionally, serum concentrations of morphine were measured in five representative patients. In the first block (n=10) a dose-response relationship for topical morphine was found. Rinses with 2 per thousand -morphine solution showed better pain relief (median 80%, range 70-80%) than those with 1 per thousand (median 60%, range 55-70%; P=0.0238). Therefore, subsequent patients enrolled for the second block (n=22) received oral rinses with 2 per thousand -morphine solution. In these patients the time to good (>or=50%) or to complete (100%) pain relief was 28 (+/-12)min after the first mouthwash, and the duration of relief was on average 216 (+/-25)min. Twenty patients (90%) received the successive mouthwashes every 3 h and 10% of them every 2 h. The duration of severe pain at the moment of swallowing was 5.17 (+/-1.47) days. Only six patients needed supplementary analgesia, and the time elapsed before the first supplemental analgesic was 1.18 (+/-0.8) days. The duration of severe functional impairment was 1.52 (+/-1.31) days, thus allowing us to feed the patient by mouth with liquid-food supplementation. During our experiment no systemically active detectable concentrations of morphine were found (GC-MS analysis). The most important side effect attributable to morphine mouthwashes was burning/itching sensation (very mild to mild intensity). Patients with painful chemoradiotherapy-induced stomatitis could be alleviated using topical morphine mouthwashes.

Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.

An acute massive epidemic of arsenic poisoning in Argentina involved 718 subjects. Urine samples were obtained from 307. The 49 with urine arsenic 76-500 micrograms/dl and 12 with urine arsenic greater than 500 micrograms/dL received dimercaprol treatment. Symptomatology increased with the urine arsenic with increased diarrhea, vomiting and systemic symptoms at urine arsenic greater than 75 micrograms/dL.

The presence of ecgonine in urine has been proposed as an appropriate marker of cocaine use. Only a few methods have been published for their determination along with cocaine and the rest of its metabolites. Due to their high polarity and consequent solubility in water, these have low recoveries, which is why it is necessary to increase the sensitivity, by the formation of hydrochloric salts or multiderivatization of the analytes or by performing two solid‐phase extractions (SPEs), considerably increasing the time and cost of the analysis. This work describes a fast and fully validated procedure for the simultaneous detection and quantification of ecgonine, ecgonine‐methyl‐ester, benzoylecgonine, nor‐benzoylecgonine, m‐hydroxybenzoylecgonine, cocaethylene, cocaine, norcocaine, and norcocaethylene in human urine (500 μL) using one SPE and simple derivatization. Separation and quantification were achieved by gas chromatography–electron ionization–mass spectrometry (GC–EI–MS) in selected‐ion monitoring mode. Quantification was performed by the addition of deuterated analogs as internal standards. Calibration curves were linear in the adopted ranges, with determination coefficients higher than 0.99. The lower limits of quantification ranged from 2.5 to 10 ng/mL. The intra‐ and inter‐day precision, calculated in terms of relative standard deviation, were 1.2%–14.9% and 1.8%–17.9%, respectively. The accuracy, in terms of relative error, was within a ± 16.4% interval. Extraction efficiency ranged from 84% to 103%. Compared with existing methods, the procedure described herein is fast, since only one SPE is required, and cost‐effective. In addition, this method provides a high recovery for ecgonine, resulting in a better alternative to the previously published methods.

The medicinal use of cannabis oil is increasing all over the world. Few analytical methods for the quantification of cannabinoids have been validated using internationally accredited guidelines. This work describes the development and validation of a selective and sensitive gas chromatography-mass spectrometry method for the qualitative analysis of the main cannabinoids, namely cannabidiolic acid, tetrahydrocannabinolic acid, cannabigerol, and cannabichromene as well as quantitative determination of cannabidiol, Δ9-tetrahydrocannabinol, and cannabinol, present in cannabis oils. The method was fully validated according to Food and Drug Administration and International Conference on Harmonization guidelines. A linear range of 0.1–30 μg/mL was obtained for CBD and Δ9-THC and 0.034–11.7 μg/mL for CBN, presenting determination coefficients above 0.99. The lower limits of quantification ranged from 0.034 to 0.1 μg/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 3.9–13.8 and 4.7–14.1%, respectively. Extraction efficiency at lower limits of quantification was 95–103%. Verification of method validity was performed with authentic cannabis oil samples. To our knowledge, this is the first method available in Argentina, validated according to international guidelines, for quantification of CBD, Δ9-THC, and CBN in cannabis oil. The primary application of this method is to differentiate between cannabis oils with high or low content of Δ9-THC, CBD, or mixed Δ9-THC/CBD. This is of fundamental importance for the patient and so that the physicians can carry out a suitable therapy.