title: Where clinical chemistry meets medicinal chemistry. Systematic analysis of physico-chemical properties predicts stability of common used drugs in gel separator serum tubes.
abstract: BACKGROUND
  As LC-MS/MS techniques are becoming more accessible even outside of highly specialized clinical laboratories, pre-analytical issues such as drug stability during specimen storage should be critically evaluated before implementing therapeutic drug monitoring. Our study investigated the influence of physico-chemical properties of different drugs in regard to their interaction with gel separators used in commercial available collection tubes.
  
  
  METHODS
  Drug spiked blood samples were analyzed after storage in different commercial gel- and non-gel based serum tubes. LC-ESI-MS/MS based methods were used to determine drug concentration in serum samples.
  
  
  RESULTS
  Lipophilic compounds, defined by logP>3 and a compatibility factor>20 are prone to be efficiently and rapidly absorbed by lipophilic gel barriers inducing a significant in-vitro decrease of drug concentration over a short storage time. Our data show a relevant drop of concentration of posaconazole, sertraline and citalopram when stored in gel based tubes. Molecular descriptors such as logP, polar surface area and protein binding seem to be good predictive markers to identify gel interacting drugs.
  
  
  CONCLUSIONS
  For ease of handling and minimization of blood drawing times, we assume that tubes containing separator gel can be used for therapeutic drug monitoring of high hydrophilic drugs. In contrast lipophilic compounds showing logP higher than 3 and/or CF>20 should be critically considered and validated by extensive stability studies.
  
  
  BACKGROUND
  logP, partition coefficient; PSA, polar surface area; TDM, therapeutic drug monitoring; ACN, acetonitrile; MeOH, methanol; IVD, in-vitro diagnostic; CF, compatibility factor.
authors: Kantonsspital Aarau, Institute of Laboratory Medicine, Tellstrasse 1, CH-5001 Aarau, Switzerland. Electronic address: christian.steuer@pharma.ethz.ch.
authors: Christian
authors: C
authors: Steuer
authors: Kantonsspital Aarau, Institute of Laboratory Medicine, Tellstrasse 1, CH-5001 Aarau, Switzerland.
authors: Andreas R
authors: AR
authors: Huber
authors: Kantonsspital Aarau, Institute of Laboratory Medicine, Tellstrasse 1, CH-5001 Aarau, Switzerland.
authors: Luca
authors: L
authors: Bernasconi
mesh_terms: D001800:Blood Specimen Collection / Q000295:instrumentation*; D002624:Chemistry, Clinical; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D004355:Drug Stability; D005782:Gels; D006801:Humans; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D005782:Gels; D004364:Pharmaceutical Preparations
keywords: Gel separator tubes; Physico-chemical properties; Stability; Therapeutic drug monitoring; logP