Development and Validation of Chiral HPLC Method for Quantification of 3-(S)-Quinuclidinol in Pharmaceutically Important Precursor, 3-(R)-Quinuclidinol, by Precolumn Derivatization

Abstract

A sensitive and specific high-performance liquid chromatography (HPLC) method for the separation and quantification of 3-(S)-quinuclidinol in 3-(R)-quinuclidinol, precursor for active pharmaceutical ingredients (solifenacin, revatropate and talsaclidine), has been developed and validated by precolumn derivatization. Several chiral columns were tested in a normal phase system. Excellent enantioseparation with the resolution more than 11.4 was achieved on Chiralpak IC column using isocratic mobile phase consisting of n-hexane, ethanol, 2-propanol and diethylamine (80:8:12:0.4, v/v). The detection was carried out using UV detector at 230 nm. The influence of mobile phase composition, namely organic modifiers, additives, aliphatic alkanes and water content in mobile phase, on retention and enantioseparation was studied. Validation of the developed method including specificity, system suitability, limit of detection, limit of quantification, linearity, repeatability, intermediate precision, accuracy and solution stability was performed according to the International Conference on Harmonization guidelines. The advantage of the method is a good HPLC enantioseparation by precolumn derivatization using reaction mixture as sample, simpler UV detection, short analysis time (<30 min), and therefore this method is suitable option for routine quantification of 3-(S)-quinuclidinol in 3-(R)-quinuclidinol.

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…have also been determined, especially in commercial products or biological samples (pharmaceutical formulations, human urine, human or animal blood, human plasma, animal serum, etc.). Another heterogeneous group of analytes, including connectors for building metal-organic frameworks [116,117,124], intermediates for the synthesis of pharmaceuticals [111], natural and synthetic compounds [39,113,121,120], biological compounds [82,112,58,71,78,86,[61][62][63]77,75], natural alkaloids [121], biomolecules [115,54], organometallic compounds [119] and chiral metabolites [103,108,100,97,102,59,63,52] has been enantioseparated with these immobilized polysaccharides CSPs (see Table 2-4). Fig.…”

“…The additives are usually used at very low proportion (0.05-0.5%, v/v) and include mainly diethylamine (DEA), triethylamine (TEA), isopropylamine (iPA), 2-aminoethanol (AE), ethylenediamine (EDA) or trifluoroacetic acid (TFA), acetic acid (AA) and formic acid (FA). Among the basic additives, DEA is the most commonly used and has proved to be effective for screening and method development of many basic compounds [40,50,51,67,68,60,74,73,55,84,95,111,58,78,62,75,122,87,93,80] (see Tables 2-4). As a general rule, basic additives are employed for enantiomer separation of basic compounds, while acidic additives are essential for acidic ones.…”