pyrimidinones and potassium-phosphate

Several related substances (RS4-RS10) were detected in lopinavir drug substance at levels ranging from 0.03% to 0.1% by employing gradient RP-HPLC. The related substances were identified by LC-MS analysis. These related substances were isolated and characterized by Mass, (1)H NMR and FT-IR spectral data. The separation was achieved on a YMC Pack ODS-AQ (250 mm x 4.6 mm, 5 microm) column thermostated at 45 degrees C using 0.02 M KH(2)PO(4) (pH 2.5): acetonitrile as a mobile phase in gradient elution mode. A PDA detector set at 210 nm was used for detection. The investigated validation elements showed the method has acceptable specificity, accuracy, linearity, precision, robustness and high sensitivity with detection limits and quantitation limits ranging from 0.028 microg/ml to 0.063 microg/ml and 0.084 microg/ml to 0.192 microg/ml respectively. The method can be used for routine quality control analysis and stability testing of lopinavir drug substance.

Topics: Buffers; Chromatography, High Pressure Liquid; Drug Contamination; Drug Stability; Guidelines as Topic; HIV Protease Inhibitors; Hydrogen-Ion Concentration; Lopinavir; Mass Spectrometry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmaceutical Preparations; Phosphates; Potassium Compounds; Pyrimidinones; Quality Control; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Temperature; Time Factors; Water