ABSTRACT
AIM To prepare the chrysin-phospholipid complex and to investigate its pharmacokinetic behaviors.METHODS Solvent evaporation method was used for preparing the complex.With preparation temperature,preparation time,chrysin concentration and drug-lipid ratio (chrysin-phospholipid) as influencing factors,together with recombination rate as an evaluation index,the preparation was optimized by orthogonal test.The obtained complex was analyzed by X-ray diffraction,differential scanning calorimetry,1H-NMR and 31P-NMR,whose solubility was examined as well.SD rats were intragastrically administered with chrysin and its phospholipid complex,respectively.The blood concentration of chrysin was detected by HPLC,after which the pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 40 ℃ for preparation temperature,2 h for preparation time,20 mg/mL for chrysin concentration,and 1 ∶ 2 for drug-lipid ratio,the recombination rate was close to 100％.Chrysin existed in an amorphous state in the phospholipid complex,which was a new phase rather than physical mixture (chrysin-phosphatidylcholine),and no new chemical bond was generated.Phospholipid complex could significantly increase chrysin's apparent solubility in water and n-octanol,the Cmax,AUC0-t and AUC0-∞ were also obviously increased as compared with raw medicine.CONCLUSION Phospholipid complex can improve both the solubility of chrysin and its oral bioavailability.
ABSTRACT
Objective To establish a rapid and accurate method for quantitative determination of erlotinib hydrochloride by proton nuclear magnetic resonance(1H-NMR). Methods Maleic acid was used as an internal standard,and DMSO-d6 was employed as solvent.The pulse width was 9.54 μs,the delay time was 20 s,the scanning frequency was 64 and the testing temperature was set as 300℃.Under this condition,the 1H-NMR data of the mixture of erlotinib hydrochloride and maleic acid were obtained.The content of erlotinib hydrochloride was calculated by comparing the response signal area of sample (As) and internal standard (Ar). Results Proton signal peaked at δ 8.84 and δ 8.47 for erlotinib hydrochloride and at δ6.26 for maleic acid served as quantitation peaks.The content of erlotinib hydrochloride was obtained by calculating the average of the test results of the two quantitative peaks.The concentration of erlotinib hydrochloride (2.88~19.08 mg·mL-1) and the peak area of quantification peaks showed a good linear correlation.The precision RSD was 0.36% (n=6),the repeatability RSD was 0.83%(n=6) and the sample recovery was 100.91% (n=6).The content of 3 batches of erlotinib hydrochloride was 92.26%,91.94%and 92.09%,the average was 92.10% and its RSD was 0.17%.The obtained results were generally consistent with those obtained from mass balance method. Conclusion This established method is simple to handle as compared to traditional methods,and the analysis results are accurate.1H-NMR provides a novel method for the determination of erlotinib hydrochloride and can be used for the quality control of erlotinib hydrochloride.
ABSTRACT
Objective To establish a novel method to determine the absolute content of quercetin by proton nuclear magnetic resonance (qNMR).Methods DMSO-d6 was employed as solvent,and maleic acid as an internal standard.Proton signal peaks at δ7.50-7.58 and δ6.26 of maleic acid were served as quantification peaks.The content of quercetin is determined with qNMR in comparison with the results obtained by mass balance method.Results Linear regression of quantitative peak areas ratio (As/Ar) of quercetin-maleic acid vs mass ratio (ms/mr) yielded a correlation coefficient of 0.999 3 and a regression equation ofy =2.963 x + 0.134 1.The contents of three batches quercetin were 85.20％,84.93％,and 85.27％,the average was 85.13％ and its RSD was 0.21％.The results were generally consistent with that of mass balance methods.Conclusion This method was easy and simple to handle,and the analysis results were accurate.It could be the complementary for the mass balance method.