ABSTRACT
OBJECTIVE: To establish a principal component reference substances external standard method with correction factor for the determination of impurity diketoal dehyde (DKA) in diketo aldehyde(DHA) bulk drug by selecting suitable liquid phase conditions. METHODS: The chromatographic C18 column (4.6 mm×250 mm, 5 μm) was used; isometric elution was set at conducted using acetonitrile-water (37∶63) as elution condition; the flow rate was 1 mL•min-1; the detection wavelength was 216 nm; the column temperature was maintained at 15 ℃; the injection volume was 20 μL. RESULTS: The DHA α peak and its impurity DKA were well separated. The average correction factor was 0.256 determined by three different chromatographic columns. CONCLUSION: The correction factor of DKA in DHA is accurate and reliable. This method can be used for the quality control of DKA in DHA raw materials.
ABSTRACT
Diketo aldehyde (DKA),one of the most important impurities in dihydroartemisinin,was synthesized through reaction between dihydroartemisinin and anhydrous ferrous bromide under a N₂ atmosphere, and an HPLC method was established for the determination of DKA in bulk drug and in DHA tablet. DKA was prepared from dihydroartemisinin in the presence of FeBr₂.The chromatographic separation was achieved through an Agilent Eclise XDB-C₁₈ column (4.6 mm×250 mm,5 μm), and the optimal mobile phase consisted of acetonitrile and water in the ratio of 37:63 at flow rate of 1.0 mL·min⁻¹.The detection was carried out at 216 nm, and column temperature was 15 °C.The injection volume was 40 μL.The method featured a good linearity (=0.999 9),precision (1.0%),repeatability (1.3%),stability (DKA standards RSD=1.0% and in tablet form instability),recovery (92.88%),limits of detection (0.20 mg·L⁻¹) ,and limits of quantification (0.78 mg·L⁻¹). The result show that the content of DKA in bulk drug was 0.086 7%-2.622 9%, and the content of DKA in tablet was 0.068 3%-0.615 1%.