Determination of urinary metabolites of XLR-11 by liquid chromatography-quadrupole time-of-flight mass spectrometry.

Recently, use of novel synthetic cannabinoids has increased greatly despite worldwide efforts to regulate these drugs. XLR-11 ((1-[5'-fluoropentyl]indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone), a fluorinated synthetic cannabinoid with a tetramethylcyclopropyl moiety, has been frequently abused since 2012. XLR-11 produces a number of metabolites in common with its non-fluorinated parent analogue, UR-144 ((1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone). Therefore, it is essential to develop effective urinary markers to distinguish between these drugs. In this study, we investigated the metabolic profile of authentic human urine specimens from suspected users of XLR-11 using liquid chromatography-quadrupole time-of-flight mass spectrometry. Furthermore, we quantified four potential XLR-11 metabolites by using commercially available reference standards. In vitro metabolism of XLR-11 and UR-144 using human liver microsomes was also investigated to compare patterns of production of hydroxypentyl metabolites. Urine samples were prepared with and without enzymatic hydrolysis, and subjected to solid-phase extraction. We identified 19 metabolites generated by oxidative defluorination, hydroxylation, carboxylation, dehydrogenation, glucuronidation, and combinations of these reactions. Among the identified metabolites, 12 were generated from a cyclopropyl ring-opened XLR-11 degradation product formed during smoking. The XLR-11 metabolite with a hydroxylated 2,4-dimethylpent-1-ene moiety was detected in most specimens after hydrolysis and could be utilized as a specific marker for XLR-11 intake. Quantitative results showed that the concentration ratio of 5- and 4-hydroxypentyl metabolites should also be considered as a useful marker for differentiating between the abuse of XLR-11 and UR-144.

Arytenoid dislocation after uneventful endotracheal intubation: a case report.

Arytenoid dislocation is an unusual complication of endotracheal intubation. We reported a case of a 48-year-old female with arytenoid dislocation after uneventful endotracheal intubation, which was successfully treated with arytenoid reduction. The patient complained of persistent hoarseness until the fourth day after an uneventful gynecologic surgery under general anesthesia. On laryngoscopic examination, paralyzed left vocal cord with minimal arytenoid movement was observed. An anteromedial dislocation of the left arytenoid cartilage was suspected and surgical reduction was performed by the laryngologist. The hoarseness was immediately resolved after surgical intervention. Anesthesiologists should be careful not to cause laryngeal trauma in anesthetized patients. In addition, early diagnosis and prompt surgical reduction are essential for a better prognosis for arytenoid dislocation.

Simultaneous GC-MS determination of seven phthalates in total and migrated portions of paper cups.

Phthalate acid esters are widely used as plasticizers to impart plastic flexibility in various industrial applications. In this study, the content of seven phthalates, dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), di-(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) were determined in paper cups using gas chromatography-mass spectrometry (GC-MS). In addition, the potential migration of these seven phthalates from paper cups into various food stimulants under different conditions was evaluated. The levels of DBP, DEHA, DEHP, and DNOP were in the ranges of 0.07-3.14, 0.16-42.69, 0.45-58.56, and 0.3-2.4 mg/kg, respectively. Meanwhile, BBP, DINP, and DIDP were not detected in most of the tested samples. In the migration test, DEHA was released to 50 % ethanol and n-heptane in a time-dependent manner and the maximum migration levels were 65.62 ± 3.61 and 95.56 ± 19.76 µg/L, respectively. The release of other phthalates was very low or negligible. These results demonstrated that paper cups are not a significant source of phthalate exposure; however, DEHA could be released from paper cups into alcoholic beverages or oily liquid beverages in the human diet.

Antiinflammatory and analgesic effects of Eurycoma longifolia extracts.

Eurycoma longifolia is one of the most popular herbal medicines in Southeast Asia. The purpose of this study is to evaluate the analgesic and anti-inflammatory effects of the methanolic extract of E. longifolia roots (TA) in vivo and to investigate the underlying mechanisms. TA was tested for analgesic activity by the hot plate test and acetic acid test in mice. The anti-inflammatory effect of TA was observed in carrageenan-induced paw edema in mice. The in vitro molecular study using macrophage cells was performed to elucidate the relevant mechanism. The analgesic activity of 400 mg/kg TA was higher than that of aspirin in the hot plate test. TA also showed analgesic effects in the acetic acid test in a dose-dependent manner. In carrageenan-induced edema in mice, TA showed an anti-inflammatory effect comparable to that of diclofenac. Further in vitro molecular study using macrophage cells revealed that TA suppressed NF-κB translocation to the nucleus, leading to inactivation of the NF-κB signaling pathway and reduction in the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These results exhibited the beneficial effects of TA for alleviating pain and inflammation, which were exerted through inactivation of the NF-κB signaling pathway.