Simultaneous determination of nadolol enantiomers in human plasma by high‐performance liquid chromatography using fluorescence‐detection

Abstract

A high-performance liquid chromatographic assay is described for the separation and quantification of nadolol isomers in human plasma. The isomers were quantified using reverse-phase HPLC and fluorometric detection after derivatization with the chiral reagent R(-)-1-(naphthyl)ethylisocyanate [R(-)-NEI]. The N-isopropyl analogue (one isomer) of nadolol was used as the internal standard. The method was reproducible based on precision studies where the percent relatives standard deviation was less than 15%. The lower limit of quantitation for each isomer was 2.5 ng/mL. This method was used to evaluate the pharmacokinetic profile of nadolol isomers in human subjects following both single and multiple oral dosing.

Enantioselective high‐performance liquid chromatography of therapeutically relevant aminoalcohols as their fluorescent 1‐naphthyl isocyanate derivatives

“…Among others, 1-naphthyl isocyanate (NIC) was used for the enhancement of detection sensitivity in TLC (Wintersteiger and Wenninger-Weinzierl, 1981) and HPLC (Wintersteiger et al, 1982;Andersson et al, 1984;Noctor, 1994;Buist et al, 1998). Optically active 1-(1-)naphthylethyl isocyanate (NEIC) was used for the chiral separation of different drugs, amongst them b-blockers (Gübitz and Mihellyes, 1984;Jira et al, 1991;Laethem et al, 1993;Belas et al, 1995), mexiletine (Freitag et al, 1993) and mefloquine (Souri et al, 1997). The naphthyl moiety was also introduced in order to increase the interactions during chromatography of enantiomers via p-p-interactions.…”

Preparation of 2R, 3S, 2′R-nadolol enantiomer using S-(-)-menthyl chloroformate as a chiral derivatizing reagent

“…Nadolol racemate A was separated its corresponding enantiomers, RSR-nadolol and SRS-nadolol, racemate B was separated into RRS-nadolol and SSR-nadolol using Chiralcel OD column (Aboul-Enein and Abou-Basha, 1996;AboulEnein, 2001). Nadolol diastereomers in plasma were extracted by solid phase extraction method (Hoshino et al, 1994b;Belas et al, 1995) or extracted by liquidliquid extraction method and derivatized with chiral derivatizing reagent R-(-)-1-(1-naphthyl)ethylisocyanate to form urea derivatves followed by determined by achiral reversed phase HPLC. And this method was applied to the bioequivance of two tablet formulations of nadolol using single and multiple dose datas from stereospecific and nonstereospecific assay (Srinivas et al, 1996).…”

Cromatografia líquida com fase quiral aplicada na separação enantiomérica de fármacos cardiovasculares

“…Os β-bloquedores representam o grupo de fármacos dos mais importantes e mais prescritos devido ao fato de que as doenças cardiovasculares estão entre as maiores causas de mortalidade mundial (Belas et al, 1995;. Atenolol, betaxolol, metoprolol, nadolol e pindolol são agentes bloqueadores de receptores β-adrenérgicos empregados principalmente, na angina pectoris, hipertensão, certas arritmias cardíacas e no tratamento do glaucoma (Darmon, Thenot, 1986;Foye, 1989;Hoffman, Lefkowitz, 1996;Krstulovic et al, 1988;Mehvar, Brocks, 2001;Srinivas et al, 1996;Zhang, Stewart, Ujhelyi, 1995).…”

“…Suas estruturas químicas podem ser vistas na Figura 1, onde pelo menos um centro quiral está presente na porção α-hidroxietilamina (aminoálcool). Faz exceção o nadolol, que possui três centros quirais (Belas et al, 1995;Mehvar, Brocks, 2001;Srinivas et al, 1996;Aboul-Enein, AbouBasha, 1996). A maioria dos agentes β-bloqueadores freqüentemente prescritos é formulada e comercializada na forma racêmica, embora, para alguns deles, já tenha sido demonstrado que o enantiômero (S)-é o responsável pelo efeito farmacológico principal (Mehvar, Brocks, 2001).…”