ABSTRACT
@#Using high performance liquid chromatography and high resolution orbital trap mass spectrometry, a two-dimensional online desalting detection method was established to determine the structure of the impurities detected under the official testing conditions of lansoprazole enteric solution preparation, and a chromatographic method compatible with mass spectrometry was established to determine and presume the structure of the impurities that could not be separated by the the official testing method.The identification of impurity was to presume its structure according to the presence of impurity reference product, so as to investigate the difference of impurity spectrum of products from different manufacturers.The one-dimensional chromatographic conditions for the 2D online desalting method were the same as those in China Pharmacopoeia (2020) under relevant substances.Two-dimensional chromatography was performed on a Waters C18 T3 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid in water-acetonitrile mobile phase and gradient elution.The chromatographic conditions for the compatible mass spectra were based on an Agilent Extend C18 (4.6 mm × 150 mm, 5 μm) column with mobile phase A: 25 mmol/L ammonium acetate and B: 25 mmol/L ammonium acetate-acetonitrile (1∶4) [pH adjusted to 6.5 with glacial acetic acid], with gradient elution. Nine impurities were detected by two-dimensional online desalting method, with 5 known impurities (A-E) and 4 unknown ones.14 impurities were detected by the compatible mass spectrometry method, with 9 unknown impurities (4 consistent with the results of two-dimensional online desalting method, and 5 newly detected).The structures and sources of the unknown impurities were deduced.The two detection methods of lansoprazole preparation by high-performance liquid chromatography-high resolution orbital trap mass spectrometry have guiding significance for quality control and process evaluation.
ABSTRACT
@#To improve the oral bioavailability of insulin, an insulin-loaded enteric polymer-lipid hybrid nanoparticles(INS-NPs L100)was prepared using methoxy PEG-poly(D, L-lactide)(PEG-PLA), phospholipid s75 and Eudragit L100; in vitro and in vivo behaviors of INS-NPs L100 were evaluated. Insulin-loaded polymer-lipid hybrid nanoparticles(INS-NPs)were prepared by W/O/W double emulsion solvent evaporation method. INS-NPs formulation was optimized by single factor experiment using encapsulation efficiency, particle size, and in vitro release behavior of the corresponding INS-NPs L100 as evaluation indexes. The morphology, in vitro drug release profile and hypoglycemic effect of the INS-NPs L100 using the optimal INS-NPs and Eudragit® L100(used as enteric polymer)were assessed. The results showed that the encapsulation efficiency of the optimal INS-NPs was(62. 18±4. 51)%. The average particle size, PDI and Zeta potential was(225. 2±94. 3)nm, 0. 191±0. 068, and -(14. 84±1. 26)mV, respectively. The cumulative drug release from the INS-NPs L100 was only 8. 01% at 2 h in pH 1. 0 HCl solution, exhibiting a slow drug release behavior; while the drug release from INS-NPs L100 was 67. 31% at 6 h in phosphate buffer of pH 6. 8. Mereorer, after oral administration of INS-NPs L100 with a dose of 38 IU/kg, the blood glucose concentration of healthy rats was reduced to 76% of the initial values at 3. 5 h, exhibiting a sustained hypoglycemic effect. In summary, the INS-NPs L100 prepared in this study could effectively decrease the release rate of insulin in gastric juice, improve the stability of protein in the gastrointestinal tract, and provide a new approach for the oral administration of peptides and protein drugs.