20.500.12556/DKUM-67425 Determination of candesartan in human plasma with liquid chromatography - tandem mass spectrometry A sensitive, specific and rapid liquid chromatography - tandem mass spectrometry method was developed and validated for the determination of candesartan in human plasma. Analyte was separated from endogenous components present in plasma by solid phase extraction. Chromatographic separation was performed on Gemini C18 analytical column using mobile phase acetonitrile – 5 mM ammonium formate pH 2 (90:10, v/v) at flow rate of 0.3 mL/min. For detection, tandem mass spectrometry in SRM mode with positive electrospray ionization was used. The mass transitions m/z 441.1 > 263.1 and 445.1 > 267.1 were used to determine candesartan by using candesartan-d4 as an internal standard. After development, the method was validated according to the requirements of EMA regulatory guidelines in the concentration range 1 - 400 ng/ml in human plasma. Limit of quantification (LLOQ) was 1 ng/ml. The developed and validated method proved to be very fast and reproducible and was therefore successfully implemented in pharmacokinetic and bioequivalence studies with large number of study samples. Za določevanje kandesartana v humani plazmi smo razvili in validirali LC-MS/MS metodo in dokazali, da je selektivna, občutljiva in ponovljiva. Za pripravo plazemskih vzorcev smo uporabili ekstrakcijo na trdni fazi. Za kromatografsko separacijo smo uporabili kolono Gemini C18 z mobilno fazo acetonitril – 5 mM amonijev formiat (90:10, v/v) pri pretoku 0,3 ml/min. Za detekcijo smo uporabili tandemsko masno spektrometrijo v SRM načinu z uporabo pozitivne ionizacije z elektro razprševanjem. Uporabljeni so bili masni prehodi: za kandesartan m/z 443,1 > 263,1 in za kandesartan-d4 kot interni standard 445,5 > 267,1. Po končanem razvoju smo metodo validirali v koncentracijskem območju 1–400 ng/ml v vzorcih humane plazme. Spodnja meja kvantitativne določitve je bila 1 ng/ml. Razvita in validirana metoda se je izkazala za zelo učinkovito pri farmakokinetičnih študijah. candesartan liquid chromatography tandem mass spectrometry human plasma kandesartan tekočinska kromatografija tandemska masna spektrometrija človeška plazma true false true Angleški jezik Slovenski jezik Znanstveno delo 2017-08-17 12:47:03 2017-08-17 12:48:22 2022-08-01 13:57:35 2019-07-11 16:19:57 2016 0 0 str. 38-46 št. 1 Letn. 63 2016 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1318-0207 543.544.5 14086149 1536821699 10.17344/acsi.2015.1836 1318-0207 URN:SI:UM:DK:QC9RBESG Acta_Chimica_Slovenica_2016_Forjan_et_al._Determination_of_Candesartan_in_Human_Plasma_with_Liquid_Chromatography_–_Tandem_Mass_Spectrom.pdf Acta_Chimica_Slovenica_2016_Forjan_et_al._Determination_of_Candesartan_in_Human_Plasma_with_Liquid_Chromatography_–_Tandem_Mass_Spectrom.pdf 1 F89C8825CD8F11ED00C83A48B440704B 3a79927599d6f24f91f2f0d23af0c1fda5a0a9f36972bf69e5d44e9e3b5f7638 85dd15a8-7c0e-11eb-bb7a-00155d0001ca 20.500.12556/dkum/669046f0-c2ff-4629-afeb-8268dc8968a0 https://dk.um.si/Dokument.php?lang=slv&id=115444 https://journals.matheo.si/index.php/ACSi/article/view/1836 1 https://dk.um.si/Dokument.php?lang=slv&id=115443 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0