title: Determination of diclofenac concentrations in human plasma using a sensitive gas chromatography mass spectrometry method.
abstract: BACKGROUND
  A gas chromatography mass spectrometry (GCMS) method for the determination of diclofenac in human plasma has been developed and validated.
  
  
  RESULTS
  This method utilizes hexane which is a relatively less toxic extraction solvent compared to heptane and benzene. In addition, phosphoric acid and acetone were added to the samples as deproteination agents, which increased the recovery of diclofenac. These revised processes allow clean extraction and near-quantitative recovery of analyte (approx. 89-95 %). Separation was achieved on a BP-1 column with helium as carrier gas. The molecular ion peaks of the indolinone derivatives of diclofenac ion (m/z 277) and the internal standard, 4-hydroxydiclofenac ion (m/z 439) were monitored by a mass-selective detector using selected ion monitoring (SIM) mode. The linear range for the newly developed and highly sensitive assay was between 0.25-50 ng/mL. The detection and lower quantifiable limits were 0.125 and 0.25 ng/mL, respectively. The inter-day and intra-day coefficients of variation for high, medium and low quality control concentrations were less than 9 %. The robustness and efficacy of this sensitive GCMS method was further demonstrated by using it for a pharmacokinetic study of an oral dosage form of diclofenac, 100 mg of modified-release capsules (Rhumalgan XL), in human plasma.
  
  
  CONCLUSIONS
  This method is rapid, sensitive, specific, reproducible and robust, and offers improved sensitivity over previous methods. This method has considerable potential to be used for detailed pharmacokinetics, pharmacodynamics and bioequivalence studies of diclofenac in humans.
authors.affiliation: Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, UAE.
authors.forename: Iltaf
authors.identifier: 0000-0002-3739-6083
authors.initials: I
authors.lastname: Shah
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE UK.
authors.forename: James
authors.initials: J
authors.lastname: Barker
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE UK.
authors.forename: Declan P
authors.initials: DP
authors.lastname: Naughton
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barton
authors.affiliation: Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, UAE.
authors.forename: Syed Salman
authors.initials: SS
authors.lastname: Ashraf
keywords: Diclofenac sodium; GCMS; Human plasma; Sensitive GCMS