Pharmacokinetic profiling via dried blood spot sampling method

PELCOVÁ, Marta, Eva KREJČÍŘOVÁ, Jan JUŘICA and Zdeněk GLATZ. Pharmacokinetic profiling via dried blood spot sampling method. In Advances in Chromatography and Electrophoresis & Chiranal 2022. 2022.

Basic information

• Original name: Pharmacokinetic profiling via dried blood spot sampling method
• Name in Czech: Farmakokinetické profilování pomocí metody suché krevní kapky
• Name (in English): Pharmacokinetic profiling via dried blood spot sampling method
• Authors: PELCOVÁ, Marta, Eva KREJČÍŘOVÁ, Jan JUŘICA and Zdeněk GLATZ.
• Edition: Advances in Chromatography and Electrophoresis & Chiranal 2022, 2022.

Other information

• Type of outcome: Conference abstract
• Confidentiality degree: is not subject to a state or trade secret
• Keywords (in Czech): farmakokinetika, klozapin, suchá krevní kapka, preklinická studie
• Keywords in English: pharmacokinetics, clozapine, dried blood spot, preclinical study

Abstract

Pharmacokinetic profiles are still an inevitable part of preclinical safety studies. Nowadays, animal models are subjected to ethical standards to be carefully monitored and the principles of the 3Rs are required: replacement, reduction and refinement. Use of dried blood spot (DBS) samples, typically 20-50 µl, rather than the larger blood volumes required to obtain plasma samples, fully embraces the latter two principles of reduction and refinement. We optimized and validated RP-HPLC method (Kinetex C18 column, 100x3.0 mm, 2.6 μm, Phenomenex) hyphenated to mass spectrometry (maXis impact qTOF, Bruker Daltonics) for the determination of two antipsychotics (namely olanzapine and clozapine) and an antidepressant (mirtazapine) in rat DBS samples. The developed LC-MS method offers short analysis cycle time (13 min) with satisfactory sensitivity covering concentration range expected for a pharmacokinetic profile at chosen drug dose. DBS samples for all time points were acquired from just one body, quantified and resultant profiles were figured.

Abstract (in Czech)

Famakokinetický profil léčiva je stále nedílnou součástí preklinických studií. V současnosti preklinické studie na zvířatech jsou podrobně sledovány a podléhají principům 3R, tj. náhrada jinou metodou, snížení počtu zvířat a zjemnění bolesti. Užití metody suché krevní kapky s typickým odběrem 20-50 ul krve je ve shodě s principy snížení a zjemnění bolesti. Optimalizovali a validovali jsme RP-HPLC metodu s hmotnostně spektrometrickou detekcí pro stanovení dvou antipsychotik (olanzapin a klozapin) a antidepresiva ( mirtazapin) v suché krevní kapce krysí krve. Vzvinutá LC-MS metoda nabíyí krátký čas analýzy s dostatečnou citlivostí pokrývající koncentrační rozsah očekávaný při zvolené dávce zvoleného léčiva (klozapin). Všechny DBS vzorky byly odebrány z jednoho jediného těla pokusného zvířete, kvantifikovány a byl získán výsledný profil a odpovídající fakmakokinetické parametry.

Abstract (in English)

Pharmacokinetic profiles are still an inevitable part of preclinical safety studies. Nowadays, animal models are subjected to ethical standards to be carefully monitored and the principles of the 3Rs are required: replacement, reduction and refinement. Use of dried blood spot (DBS) samples, typically 20-50 µl, rather than the larger blood volumes required to obtain plasma samples, fully embraces the latter two principles of reduction and refinement. We optimized and validated RP-HPLC method (Kinetex C18 column, 100x3.0 mm, 2.6 μm, Phenomenex) hyphenated to mass spectrometry (maXis impact qTOF, Bruker Daltonics) for the determination of two antipsychotics (namely olanzapine and clozapine) and an antidepressant (mirtazapine) in rat DBS samples. The developed LC-MS method offers short analysis cycle time (13 min) with satisfactory sensitivity covering concentration range expected for a pharmacokinetic profile at chosen drug dose. DBS samples for all time points were acquired from just one body, quantified and resultant profiles were figured.

Links

• MUNI/G/1464/2018, interní kód MU: Name: Nové směry v bioanalytických přístupech pro personalizovanou farmakoterapii schizofrenie (Acronym: TDM olanzapinu v DBS)

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects