LC–MS/MS assay for assessing medical adherence in patients under warfarin maintenance therapy

Faten Farouk*, Samir Nabhan, Wilfried M.A. Niessen, Hassan M.E. Azzazy

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Warfarin (WRN) use is plagued by response fluctuation which is managed by dose adjustment. The plasma WRN level had always been an abandoned prerequisite for dose adjustment. However, recent reports had correlated WRN level to the consumed dose. More importantly, the intra-individual alteration in WRN level was found proportional to response fluctuation. This renewed the interest to use WRN level prior to dose adjustment to account for dispensing errors or inadequate adherence. Detection of possibly interacting drugs may further assess compliance and enable a wiser dose adjustment. In this study, an LC–MS/MS assay was developed and validated for the determination of the WRN and the simultaneous detection of interacting drugs in citrated plasma samples normally collected for monitoring international normalized ration (INR). Samples were prepared by liquid-liquid extraction. Separation of WRN and interacting drugs (n = 19) was achieved on an Inertsil®C18 column using a gradient elution program. The assay was applied in 96 plasma samples from patients. The developed method was linear, accurate and precise for WRN determination with average recovery of 99.5 ± 8.4% and no relative matrix effect. WRN plasma level was measured in all samples and possible interacting drugs were detected. An improved WRN-response correlation was observed inter-individually when patient variability was reduced. Our results support the significance of WRN monitoring and suggest the additional monitoring of other interacting drugs for integrated evaluation of patient adherence. The developed method enables ruling-out inadequate adherence prior to unnecessary dose adjustment and highlights the need to strengthen patient education procedures.

Original languageEnglish
Pages (from-to)135-140
Number of pages6
JournalMicrochemical Journal
Early online date3 May 2018
Publication statusPublished - Sept 2018


  • Drug-drug interaction
  • Patient compliance
  • Therapeutic drug monitoring
  • Warfarin dose adjustment


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