147762-57-0

Tramadol (T) is available as a racemic mixture of (+)-trans-T and (-)-trans-T. The main metabolic pathways are O-demethylation and N-demethylation, producing trans-O-desmethyltramadol (M1) and trans-N-desmethyltramadol (M2) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)-trans-T and (+)-M1 and to the monoaminergic action of (+/-)-trans-T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis of trans-T, M1, and M2 enantiomers. The analytes were resolved on a ChiralpakA AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml for trans-T and M1 and 0.1 ng/ml for M2. The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n = 6 at each time point) received a single oral dose of 20 mg/kg racemic trans-T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition of trans-T and M2 was enantioselective (AUC(+)/(-) ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics of trans-T and M2 in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies of trans-T pharmacokinetics. Chirality, 2011.

In the present study the transformation and mineralization of a common aquatic pollutant, Tramadol (TRA) was investigated for the first time by means of TiO2 photocatalysis. The degradation kinetics for both TRA and total organic carbon (TOC) followed apparent first-order model with rate constants of k = 15.3 10 min and k = 9.7 10 min and half lives (t) of 4.5 min and 71.4 min, respectively. The transformation products (TPs) of TRA, were identified by high resolution accurate mass liquid chromatography (HR-LC-MS) suggesting that hydroxylation, oxidation and dealkylation are the main transformation pathways. The reactions were found to occur mainly at the surface of the photocatalyst via surface-bound HO radicals rather than by free diffusion into the homogeneous phase. The potential risk of TRA and its TPs to aqueous organisms was investigated using Microtox bioassay before and during the process. The acute toxicity increased in the first stages and then decreased rapidly to very low values within 120 min of the photocatalytic treatment. The increase in the toxicity is associated with near additive or low synergistic effects between two TPs generated during the process i.e. N-desmethyl and N-oxide tramadol.

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of fibromyalgia, restless leg syndrome may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of motor neurone disease, diabetic neuropathy, postherpetic neuralgia, acute opioid withdrawal management, obsessive-compulsive disorder, premature ejaculation, PTSD, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, bipolar depression, depression, stress, cancer pain and lower back pain.