Chiral supercritical fluid chromatography/tandem mass spectrometry for the simultaneous determination of pindolol and propranolol in metabolic stability samples

Abstract

A chiral packed-column supercritical fluid chromatographic (pSFC) system coupled to tandem mass spectrometer (MS/MS) for the rapid measurements of (R,S)-propranolol and (+/-)-pindolol in metabolic stability samples was developed. The effects of the eluent flow rates and compositions, as well as of the nebulizer temperature, on the chromatographic performance and the ionization efficiency of the analytes in positive ion mode under pSFC conditions were studied. The ionization mechanism of the analytes in the CO2/methanol atmospheric pressure chemical ionization (APCI) environments with or without the use of an additive was studied. The chiral pSFC-APCI-MS/MS approach requiring approximately 2 min per sample was applied for the simultaneous determination of two pairs of racemic drugs in in vitro samples at low nanogram per milliliter concentrations.

Supercritical fluid chromatography‐mass spectrometry for chemical analysis

“…For the chromatographic resolution of chiral compounds, SFC was proven to provide at least two times faster separation than normal-phase HPLC [36,37]. As an example, a chiral packed-column SFC system linked with APCI-MS was reported for the simultaneous determination of (R,S)-propranolol and (+)-pindolol in metabolic stability samples and mouse blood samples [28,29] (Fig. 2).…”

Chiral separations in sub‐ and supercritical fluid chromatography

“…Possibly, the method can also be extended to permeability, hepatocyte stability, and protein-binding assays. In a next study [40], the set-up of [39] was used to determine propranolol and pindolol enantiomers in mouse blood. Besides the effects of flow rate and mobile phase composition on the separation, the influence of DEA or isopropylamine as additives was investigated.…”

“…A chiral SFC-tandem mass spectrometric method was developed for the simultaneous determination of pindolol and propranolol in metabolic stability samples [39]. The mass spectrometer used an APCI ionization source, and detection was performed in the positive ion mode.…”

Supercritical Fluid Chromatography

“…With its distinct advantages in analysis speed, SFC, especially combined with mass spectrometers, has been increasingly recognized as a very effective tool for highthroughput analysis. Hsieh et al (2005) studied the effects of the nebulizer temperature, eluant fl ow rates, and compositions on the chromatographic performance and ionization effi ciency of analytes in positive ion mode under packed column SFC conditions. A higher percentage of modifi er caused loss of the relative APCI response.…”