Determination of tramadol and its active metabolite O-desmethyltramadol in plasma and amniotic fluid using LC/MS/MS

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Determination of tramadol and its active metabolite O-desmethyltramadol in plasma and amniotic fluid using LC/MS/MS

[Article in Chinese]

Zhao LM, Chen XY, Cui JJ, Sunita M, Zhong DF.

Laboratory of Clinical Pharmacology, China Medical University No. 2 Hospital, Shenyang 110004, China.

AIM: To determinate tramadol and O-desmethyltramadol in human plasma and amniotic fluid by LC/MS/MS, and distribution of tramadol and O-desmethyltramadol in maternity and fetus were studied. METHODS: Samples containing tramadol, O-desmethyltramadol and diphenhydramine (internal standard, IS ) were extracted using liquid-liquid extraction, followed by liquid chromatographic separation and on-line MS/MS using atmospheric pressure chemical ionization as an interface detection. The analytes were detected in the selected reaction monitoring mode. RESULTS: The calibration curves for tramadol and O-desmethytramadol in plasma and amniotic fluid were linear in the range from 8.0 to 800.0 microg x L(-1) (plasma) and 1.0 to 400.0 microg x L(-1) (amniotic fluid). The method was applied to the measurement of tramadol and O-desmethytramadol concentrations in maternal vein, umbilical vein, umbilical artery and amniotic fluid. Following intramuscular pre-operative administration 1.5 mg x kg(-1) doses of tramadol to parturients, plasma concentrations of tramadol were significantly higher than those in amniotic fluid. The concentrations of O-desmethyltramadol in plasma were lower, and were not detected in amniotic fluid. CONCLUSION: The method is shown to be accurate, robust and convenient, and suitable for clinical pharmacokinetics studies of tramadol and O-desmethyltramadol.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15491106&query_hl=2

The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats?

Combe R, Bramwell S, Field MJ.

Pain Therapeutics, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT139NJ, UK. Rachel.Combe@Pfizer.com

Osteoarthritis (OA) is a widespread condition affecting the elderly population. One of the most prominent features but least studied symptoms is chronic pain associated with OA. The study objective was to determine pain endpoints in rats with monosodium iodoacetate (MIA) induced OA, and to investigate the efficacy of common nociceptive agents. Sprague-Dawley rats received an intraarticular injection of either 25 microl 80 mg/ml MIA or 25 microl 0.9% sterile saline into the right knee joint. Changes in von Frey thresholds and latencies to stroking with a cotton bud (punctate and dynamic allodynia, respectively) were measured pre- and for up to 10 weeks post-intraarticular injection. Changes in hind paw weight distribution were also determined. Both punctate allodynia and a weight bearing deficit were observed in MIA-treated rats for up to 10 weeks. Interestingly, dynamic allodynia was not detected at any time point tested. Morphine (0.3-3 mg/kg, s.c.) and tramadol (3-100 mg/kg, p.o.) dose-dependently inhibited punctate allodynia and partially reversed weight bearing deficit. In conclusion, the MIA model of OA is reproducible and mimics OA pain in humans. Analgesic drug studies indicate this model may be useful for investigating chronic nociceptive pain.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15488329&query_hl=2

The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats.

Gotrick B, Tobin G.

Department of Hospital Dentistry, Malmo University Hospital, SE-20502 Malmo, Sweden.

Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. Currently it was examined by which principal mechanism tramadol induces oral dryness. The effects of intravenous administration (+/-)-tramadol were studied in rats on the flow of saliva in response to a peripheral cholinergic stimulus or to reflex activation involving the relay of impulses in the central nervous system. In pentobarbitone-anaesthetized rats, the salivary secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The administration alpha- and beta-adrenoceptor antagonists resulted in almost identical acetylcholine-evoked responses as in the absence of tramadol. The secretory response to the application of citric acid on the tongue of the rat was reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p < 0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating inhibitory pathways in the central nervous system and has no anticholinergic effect on the salivary glands at dosages that may be clinically relevant. Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion occurred at a glandular level and depended most likely on a release of noradrenaline from glandular nerve terminals.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15485638&query_hl=2