title: Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.
abstract: BACKGROUND
  Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone.
  
  
  METHODS
  Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI).
  
  
  RESULTS
  Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study.
  
  
  CONCLUSIONS
  Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.
authors.affiliation: .
authors.forename: Flaminia
authors.initials: F
authors.lastname: Pantano
authors.affiliation: .
authors.forename: Stefano
authors.initials: S
authors.lastname: Brauneis
authors.affiliation: .
authors.forename: Alexandre
authors.initials: A
authors.lastname: Forneris
authors.affiliation: .
authors.forename: Roberta
authors.initials: R
authors.lastname: Pacifici
authors.affiliation: .
authors.forename: Enrico
authors.initials: E
authors.lastname: Marinelli
authors.affiliation: .
authors.forename: Chrystalla
authors.initials: C
authors.lastname: Kyriakou
authors.affiliation: .
authors.forename: Simona
authors.initials: S
authors.lastname: Pichini
authors.affiliation: .
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Busardò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D010098:Oxycodone / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D010111:Oxymorphone / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D053719:Tandem Mass Spectrometry
chemical_list: D009019:Morphinans; C077256:noroxycodone; D010111:Oxymorphone; D010098:Oxycodone
keywords: noroxycodone; oxycodone; oxymorphone; ultra-high-performance liquid chromatography tandem mass spectrometry