ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers. METHODS: Sixty-nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed. RESULTS AND DISCUSSION: Large interindividual variability was observed in the tramadol-induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P < 0·05) except for the reflex amplitude and constriction velocity. WHAT IS NEW AND CONCLUSION: The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.
Subject(s)
Analgesics, Opioid/pharmacology , Cytochrome P-450 CYP2D6/genetics , Pupil/drug effects , Tramadol/pharmacology , Administration, Oral , Adolescent , Adult , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacokinetics , Biomarkers, Pharmacological/metabolism , Cytochrome P-450 CYP2D6/metabolism , Female , Humans , Male , Miosis/chemically induced , Mydriasis/chemically induced , Polymorphism, Genetic , Tramadol/administration & dosage , Tramadol/pharmacokinetics , Young AdultABSTRACT
A sensitive and selective method for screening of benzodiazepines and their metabolites in urine using liquid chromatography coupled with tandem mass spectrometric detection is presented. Analytes were separated on C18 column using gradient elution. Ionisation of analytes was performed by positive electrospray operated in Selected Reaction Monitoring mode. Optimization of the chromatographic method, acid hydrolysis and liquid - liquid extraction was also described. The limit of detection for most of analytes was 1 ng/mL. The chromatograms of real samples, which are also presented, demonstrate the selectivity, universality and simplicity of the developed method.
