Isolation and identification of minor impurities during the synthesis of vitamin K1

Determination of organic impurities in pharmaceutical preparations

“…NMR spectrometry is finding increasing application for the identification of unknown organic impurities in pharmaceutical preparations [50,60,72,[80][81][82][83][84][85]. This method is highly informative and allows conclusions to be drawn on the structure of the components in a mixture of related compounds because the form of the NMR spectrum changes on even an insignificant change in the geometry of the molecule and bond orders.…”

“…In the majority of cases, unmodified silica gel [56,[58][59][60] and silica gel with modifying amino groups [57] are used as polar sorbents for the determination of impurities by normal-phase HPLC. Nonpolar organic solvents with the addition of polar modifiers, e.g., CHCl 3 -methanolwater (4893 : 10 : 7) [58], ethanol-hexane (7 : 3) [56], hexane-ether [60], etc., are used as the mobile phase.…”

“…In some cases, impurities are identified using the chromatographic extraction of fractions containing impurities, their preconcentration with solvent replacement, and the subsequent measurement of mass spectra [50,72,90] and NMR spectra [50,60,72,80].…”

“…Normal-phase HPLC is very rarely used for the determination of organic impurities in pharmaceutical preparations [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60], because their components and impurities are commonly polar compounds. In the majority of cases, unmodified silica gel [56,[58][59][60] and silica gel with modifying amino groups [57] are used as polar sorbents for the determination of impurities by normal-phase HPLC.…”

“…It requires the use of several independent approaches. The problem can be partially solved by HPLC using the diode-array UV detector [58,[70][71][72][73][74][75], mass spectrometer (MS) [51,71,[76][77][78][79], and nuclear magnetic resonance (NMR) spectrometer [50,60,72,[80][81][82][83][84][85].…”