Determination Of The Component Content In Ofloxacin Eye Drops,Compound Valsartan Hydrochlorothiazide Tablet And Chai Huang Oral Liquid By Quantitative Nuclear Magnetic Resonance Spectroscopy With Capillary Internal Standard

Quantitative nuclear magnetic resonance spectroscopy（qNMR）using a capillary internal standard,which mixes and seals the internal standard sample with deuterium reagents in an inserted capillary,eliminates the need to weigh the internal standard and measure deuterium reagents during sample determination.It has the advantages of simple and time-saving sample preparation,saving internal standards and deuterium reagents,wide selection of sample solvents,and convenient sample recovery,and is conducive to promoting the wider application of the qNMR method.Established a method for the determination of ofloxacin in ofloxacin eye drops,valsartan and hydrochlorothiazide in compound valsartan and hydrochlorothiazide tablets,and the baicalin total flavones and sodium benzoate in Chaihuang oral liquid using qNMR with capillary internal standard.The method has been validated and can be used for the determination of the three kinds of samples.The thesis includs three parts as follows.1.A qNMR method using capillary internal standard to determinethe concentration of ofloxacin in eye drops was established.Potassium hydrogen phthalate was selected as internal standard and dissolved in deuterium reagent,sealed in a glass capillary and used to measure the correction factor k（0.03125±0.00033）by analyzing three pure products with known contentration.The method was proved to be stable and independent of the sample,allowing direct measurement of other components.For ofloxacin determination,δ1.53 ppm（H-14,d,J=6.5Hz,3H）was selected as the quantification peak,andδ7.55 ppm（d,2H）as the internal standard peak for ofloxacin determination in eye drops.The method demonstrated the RSD of0.54%for intra-day precision,the linear correlation coefficient of 0.9996,the LOD of 0.04mg/m L,and the recovery rate of 98.8%to 103.9%.Compared the capillary internal standard method with the commercial coaxial tube internal standards,the impact of capillary size on samples and internal standards was discussed.The method has been applied to determine the ofloxacin content in three batches of real ofloxacin eye drops..2.A qNMR method using capillary internal standard to determine the content of valsartan and hydrochlorothiazide in compound valsartan and hydrochlorothiazide tablets was studied.3,4,5-trichloropyridine was selected as the internal standard,and DMSO-d₆as the deuterium reagent,to be prepared the intrnal standard capillary to determine the correction factor k（0.04449±0.00054）.The NMR peak ofδ8.72-9.00 ppm（H-19-22）was selected as the quantification peak for valsartan,andδ9.33 ppm（H-8,s,1H）was selected as the quantification peak for hydrochlorothiazide.The qNMR method was validated.For valsartan and hydrochlorothiazide,the intra-day precision RSDs were 0.66%and 0.77%,and the linear correlation coefficients were 0.9998 and 0.9999,respectively.The detection limits were 0.16mg/m L and 0.02 mg/m L,and the recovery were 97.9%-101.8%and 98.9-101.4%,respectively.The method has been applied to determine valsartan and hydrochlorothiazide in three batches of the compound tablets.3.A qNMR method using capillary internal standard to determine total flavonoids（calculated by baicalin）of Scutellariae and sodium benzoate in Chai Huang oral liquid was established.3,4,5-trichloropyridine was selected as the internal standard,and solved in DMSO-d₆deuterium reagent in the internal standard capillary.The NMR peakδ6.60 ppm（H-8,1H,s）was selected as the quantification peak for total flavonoids of Scutellariae,andδ7.84 ppm（H-1,2,2H,d）as the quantification peak for sodium benzoate.The RSDs of intra-day precision for total flavonoids of Scutellariae and sodium benzoate were 0.29%and0.64%,respectively.The linear correlation coefficients were 0.9999 and 0.9996,and the LODs of detection limit were 0.02 mg/m L and 0.09 mg/m L,respectively.The recoveries were98.0%-101.8%for total flavonoids of Scutellariae and 99.9%-102.4%for sodium benzoate.The method has been applied to determine the total flavonoids of Scutellariae and sodium benzoate in three batches of Chai Huang oral liquid samples.The results show that the linearity,accuracy,precision,and content determination results of the qNMR method meet the related requirements in the pharmacopoeia when determining single components in eye drops,compound tablets,and complex Chinese medicine oral liquid samples,and suggests the qNMR method broad application prospects.