Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma

Abstract

Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded in the MRM mode by using a positive electrospray source with tandem mass spectrometry detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram (8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant concentrations for each drug. Coefficients of determination (R2 ) were higher than 0.99, while the relative difference between nominal and measured concentrations (RE) and CV were lower than 15% for all targets. High performance liquid chromatography coupled with the mass detector (HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone 366 and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy, precision, matrix effect and stability. This method has significant advantages in terms of low sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4 minutes).

Simultana kvantifikacija većeg broja psihijatrijskih lekova je važna za terapijsko praćenje psihijatrijskih pacijenata. Takođe , od značaja iz praktičnih ra zloga bi bilo da metoda bude jednostavna, laka za izvođenje i da ne zahteva puno vremena. Uz orak plazme (200 μl) je deproteinizovan i izvršeno je h romatografsko razdvajanje lekova na ZORBAX Eclipse XDB- Phenyl koloni sa mobilnom fazom sačinjenom od acetonitrila i vo denog rastvora 0,1% mravlje kiseline ( 60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i zvora sa elektrosprej pozitivnom jonizacijom i tandemske masene detekcij e. Ispitivani opseg koncentracija bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop ram, gde je bio 8-256 ng/ml. Kontrolni uzorci su pripremani u kvintuplikatu u tri relevantne koncentracije za svaki lek. Determinacioni koeficijenti (R 2 ) bili su veći od 0,99, dok su relativna razlika između nominal nih i merenih koncentracija (RV) i koeficijent varijacije (CV) bili manji od 15% za sve analite. Metoda tečne hromatografije visoki h performansi uparena sa tand em masenim detektorom (HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti , tačnosti, preciznosti, efekata matriksa i stabilnosti za simultano određivanje sertralina, escitaloprama, risperidona i paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz orka (200 μl), kratke pripreme uzorka (3 sata) i kratko vreme tr ajanja pojedinačnog merenja (4 minuta).