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Purpose Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. Methods The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 [micro]g/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. Results The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p < 0.001), and to 4 (1-8) after FENtd (p < 0.001). The effects of FENiv, as evaluated by [DELTA]NRS, CGI-I, and SS, were significantly greater than those of FENtd (p 0.04, each). Conclusions The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl., Author(s): Norihito Hayashi[sup.1] , Akifumi Kanai[sup.2] , Asaha Suzuki[sup.1] , Yuki Nagahara[sup.1] , Hirotsugu Okamoto[sup.1] Author Affiliations: (1) Department of Anesthesiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.01.013 Byline: M. Gergov, P. Nokua, E. Vuori, I. Ojanpera Keywords: Fentanyls; Opioid drugs; LC-MS/MS Abstract: A method for simultaneous screening and quantification was developed for the fentanyls alfentanil, fentanyl, p-fluorofentanyl, cis-3-methylfentanyl, trans-3-methylfentanyl, alpha-methylfentanyl, norfentanyl, remifentanil, sufentanil, and the other opioid drugs 6-acetylmorphine, buprenorphine, codeine, dextropropoxyphene, ethylmorphine, heroin, methadone, morphine, naloxone, naltrexone, norbuprenorphine, normethadone, oxycodone, pentazocine, pethidine, and tramadol in post-mortem blood and urine samples by LC-MS/MS. Samples were extracted with butyl acetate at pH 7. The drugs were separated by LC on a Genesis C.sub.18 reversed-phase column, with a gradient consisting of acetonitrile and ammonium acetate at pH 3.2. The mass spectrometric analysis was performed with a quadrupole-linear ion-trap mass spectrometer equipped with a turbo ion spray interface in positive mode using multiple reaction monitoring (MRM). Quantification was performed based on five isotope-labelled internal standards. Validation included assessment of linearity, limit of quantification, inaccuracy, precision, and matrix effects. The limits of quantification were adequate for screening and quantification of opioid drugs at low therapeutic or abuse concentration levels, with inaccuracy less than 23% and precision better than 24% both in blood and urine samples. When this method was applied to autopsy cases, its results were in agreement with those of reference methods. Author Affiliation: Department of Forensic Medicine, University of Helsinki, P.O. Box 40, FIN-00014, Helsinki, Finland Article History: Received 2 May 2008; Revised 30 December 2008; Accepted 14 January 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2008.12.019 Byline: Nelson M. Lafreniere, James H. Watterson Keywords: Forensic toxicology; Bone; Fentanyl; Drug; ELISA; Immunoassay Abstract: The detection of acute fentanyl exposure in fresh and decomposed skeletal tissues (marrow and bone), by automated enzyme-linked immunosorbent assay (ELISA) is described. Rats (n =15) were administered fentanyl acutely at a dose of 0 (n =3), 15 (n =3), 30 (n =3) or 60[mu]g/kg (n =6) by intraperitoneal injection, and euthanized within 20min. Femora and tibiae were extracted from the fresh corpses and marrow was isolated from the femoral and tibial medullary cavities. The remains were then allowed to decompose outdoors to the point of complete skeletonization, and vertebrae and pelvi were recovered for analysis. In all cases, bones were cleaned in alkaline solution and then ground into a fine powder. Marrow was homogenized in alkaline solution. Fentanyl was extracted from ground bone by methanolic extraction. Extracts were adjusted to pH 6 and analyzed by ELISA. Perimortem heart blood was also collected and diluted in phosphate buffer prior to screening by ELISA. The effect of tissue type on ELISA response was examined through determination of binary classification test sensitivity and the relative decrease in absorbance (%DA, drug-positive tissues vs drug-free controls) in each tissue type. Overall, the %DA varied significantly between extracts from different skeletal tissues under a given dose condition, according to the general order of marrowvertebrae[approximately equal to]pelviepiphyseal bone[approximately equal to]diaphyseal bone. Binary classification test sensitivity values for fentanyl in marrow, fresh epiphyseal (femoral and tibial) bone, fresh diaphyseal (femoral and tibial) bone, decomposed vertebrae and decomposed pelvic bone were 100%, 16-33%, 0-16%, 0-33% and 66-100%, respectively, at the 60[mu]g/kg dose level. While mean %DA values showed a strong positive correlation with those in marrow and blood measurements and the administered dose (r =0.997 and 0.986), such a correlation was not observed in assays of decomposed tissues (r =-0.157 and -0.315). These results suggest that the type of skeletal tissue sampled and position within a given bone may be important considerations in the choice of substrate for fentanyl screening in skeletal tissues, but that quantitative analysis of drugs in decomposed bones may be of limited interpretive value. Author Affiliation: Forensic Toxicology Research Laboratory, Department of Forensic Science, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada P3E 2C6 Article History: Received 13 October 2008; Revised 5 December 2008; Accepted 18 December 2008