C. STEUER¹, M. MOOSMANN¹, L. BERNASCONI¹, A. R. HUBER<sup>1

1</sup>Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland

Therapeutic drug monitoring is gaining more and more popularity in the clinical chemistry lab. In general, laboratory drug monitoring always correlates with the pharmacological and toxicological profile of the drug. Since using LC-MS/MS based technology in the clinical laboratory, simultaneous monitoring of different drugs is no challenge anymore. Drug monitoring helps to control the maintenance or effective dosage (immunosuppressant’s, antibiotics), the compliance of patients to the dedicated therapy (antiepileptic drugs) and alert in case of toxic levels due to wrong dosing scheme, metabolic abnormalities and co-administration of drugs (antimycotics). Developments in collection tubes and devices increase further the practicability of TDM and improve the liquid handling in the lab. But care must be taken when using gel separator tubes. Even new generation of these tubes can cause pitfalls in clinical analysis. Former studies on gel separator tubes were done without further investigation of physico-chemical properties of the drug. Mostly phenytoin and carbamazepine were used as reference compounds. According to Lipinsky`s rule of 5 for bioavailable drugs these reference compounds show an average logP and polar surface area for oral bioavailable drugs. Also high hydrophilic drugs e.g. antibiotics, were often part of these studies. It seems unlikely that polar compounds interact with lipophilic gel ingredients. Interestingly, high lipophilic drugs like posaconazol which is prone to interfere with lipophilic matrices and tissues were not investigated in these studies. Promiscuous binding is a well-known phenomenon in medicinal chemistry and should be critical investigated in the drug discovery process. LogP, polar surface area and also H-bond-donor/acceptor properties can influence this unspecific behavior of chemical entities. Combining both theories for drug discovery and clinical chemistry, we present herein a detailed investigation of physico-chemical properties of oral bioavailable drugs in relation to interferences with lipophilic aromatic polymers found in common gel separator serum tubes.