Development of electrochemical methods for determination of tramadol--analytical application to pharmaceutical dosage forms.

Delerue-Matos C.

CEQUP/Departamento Engenharia Quimica, Instituto Superior de Engenharia do Porto, Rua S. Tome, 4200-485 Porto, Portugal.

A square-wave voltammetric (SWV) method and a flow injection analysis system with amperometric detection were developed for the determination of tramadol hydrochloride. The SWV method enables the determination of tramadol over the concentration range of 15-75 microM with a detection limit of 2.2 microM. Tramadol could be determined in concentrations between 9 and 50 microM at a sampling rate of 90 h(-1), with a detection limit of 1.7 microM using the flow injection system. The electrochemical methods developed were successfully applied to the determination of tramadol in pharmaceutical dosage forms, without any pre-treatment of the samples. Recovery trials were performed to assess the accuracy of the results; the values were between 97 and 102% for both methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12899984&dopt=Abstract tramadol



Tramadol encapsulated into polyhydroxybutyrate microspheres: in vitro release and epidural analgesic effect in rats.

Aypar U.

Hacettepe University Faculty of Medicine, Department of Anaesthesiology and Reanimation, Ankara, Turkey. asalman hacettepe.edu.tr

BACKGROUND: Controlled release techniques are used to increase the duration of action and decrease the toxicity of drugs. Any controlled release form of tramadol in spinal or epidural blocks has not been studied previously. Tramadol was encapsulated into polyhydroxybutyrate (PHB) microspheres and release kinetics was studied. The epidural analgesic effect of this solution in rats was also compared with free tramadol. METHODS: Controlled release of tramadol from PHB microspheres into 10 ml of phosphate buffer solution at pH 7.4 and 37 degrees C was studied in vitro. In vivo studies were performed in 40 rats. Epidural catheters were placed during general anaesthesia. Rats were randomly allocated into one of the four study groups to receive normal saline, 4 mg of tramadol, PHB microspheres without tramadol, or 4 mg of tramadol encapsulated into PHB microspheres. Analgesia was evaluated with tail flick tests performed at 52.5 +/- 0.5 degrees C before injection and at intervals up to 30 h after injection. Catalepsy and loss of corneal reflexes were considered as signs of supraspinal toxicity. RESULTS: In vitro drug release was observed for more than 6 days. Epidural analgesic effects of tramadol released from PHB microspheres were observed for 21 h, whereas an equal dose of free tramadol was effective for less than 5 h. No signs of toxicity were observed. CONCLUSION: Controlled release of tramadol from PHB microspheres is possible, and pain relief during epidural analgesia is prolonged by this drug formulation compared with free tramadol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12904194&dopt=Abstract tramadol



Determination of tramadol in hair using solid phase extraction and GC-MS.

Abu-Ragheib S.

Forensic Medicine and Toxicology Division, Faculty of Medicine, Jordan University Hospital, University of Jordan, Amman 11942, Jordan. kahadidi yahoo.com

Tramadol is a centrally acting synthetic analgesic with mu-opioid receptor agonist activity, it is a widely prescribed analgesic used in the treatment of moderate to severe pain and as an alternative to opiates. Tramadol causes less respiratory depression than morphine at recommended doses. Its efficacy and low incidence of side effects lead to its unnecessary prescribing in patients with mild pain. Tramadol was classified as a "controlled drug" long after its approval for use in Jordan. Analysis of drugs of abuse in hair has been used in routine forensic toxicology as an alternative to blood in studying addiction history of drug abusers. A method for the determination of tramadol in hair using solid phase extraction and gas chromatography-mass spectrometry (GC-MS) is presented, the method offers excellent precision (3.5-9.8%, (M)=6.77%), accuracy (6.9-12%, M=9.4%) and limit of detection 0.5 ng/mg. The recovery was in the range of 87-94.3% with an average of 90.75%. The calibration curve was linear over the concentration range 0.5-5.0 ng/mg hair with correlation coefficient of 0.998. The developed method was tested on 11 hair samples taken from patients using tramadol as prescribed by their physician along with other different drugs in treating chronic illnesses. Tramadol was detected in all hair samples at a concentration of 0.176-16.3 ng/mg with mean concentration of 4.41 ng/mg. The developed method has the potential of being applied in forensic drug hair testing. In Jordan, hair drug testing started to draw the attention of legal authorities which stimulated forensic toxicologists in recent years to develop methods of analysis of drugs known or have the potential to be abused.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12927414&dopt=Abstract tramadol



Differential effects of lidocaine and tramadol on modified nerve impulse by 4-aminopyridine in rats.

Gocmen C.

Department of Biophysics, University of Cukurova, School of Medicine, Balcali, TR-01330 Adana, Turkey. tufanmert yahoo.com

We have used the sucrose gap method to measure the effects of drugs on the electrophysiological properties of rat sciatic nerves. The results showed that 4-aminopyridine produced a slight conduction block, prolonged the duration of action potential, enhanced the hyperpolarizing afterpotential, and elicited a hump that followed the action potential. In the presence of 4-aminopyridine, the impulse-blocking activity of lidocaine and tramadol was enhanced. Both lidocaine and tramadol effectively depressed the delayed depolarization generated by 4-aminopyridine. While tramadol decreased the activity-evoked hyperpolarizing afterpotentials, lidocaine completely removed them. These findings indicate that lidocaine may be more effective in blocking the Na(+) channels than tramadol. Tramadol may be more effective on the delayed rectifier K(+) channels than lidocaine. Copyright 2003 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12928579&dopt=Abstract tramadol