| The study prepared sarafloxacin potassium injection,and then evaluated the quality standard,stability and safety of the injection,and studied the pharmacokinetics of the injection in rats,which provided sufficient theoretical basis for the clinical application of the injection.Using high performance liquid chromatography,the content of sarafloxacin was determined at a wavelength of 274nm,which showed a good linear relationship in the range of 0.5μg/mL-8μg/mL,and the method has good specificity,high precision,RSD is less than 2%,recovery is more than 95%,and meet the detection requirements.The prepared sarafloxacin content is 93.6%,and the chloride ion content does not exceed 0.01%.Determine the best solvent and pH regulator for sarafloxacin potassium injection through single factor test,and determine the best solvent system through orthogonal test using range method for factor level analysis,the single factor test is used to determine the amount of arginine,sodium sulfite and nano-silica in the injection to determine the best prescription.The prescription is:sarafloxacin 2.5g,L-arginine 5g,EDTA 0.1g,sodium sulfite 0.2g,n-butanol 2%,benzyl alcohol 2%,nano-silica is200ppm,the pH is adjusted to 11.00,and the volume of water for injection is adjusted to 100mL.The preparation process is optimized on this basis.The best process is:mix EDTA,L-arginine,and sodium sulfite,add 50 mL of water for injection at 40°C,stir to dissolve,add benzyl alcohol and n-butanol,stir,add sarafloxacin in 3 batches,stir evenly,add nano silica,add water for injection at 40°C to 90 mL,adjust the pH to11.00 with potassium hydroxide solution,dilute the volume to 100 mL,pass through a0.2μm microporous membrane,potting,sterilize,and detect leaks to obtain sarafloxacin potassium injection.Through the inspection of visible foreign matter,pH and content of the injection,the results show that the injection has no visible foreign matter,the pH is between 10.50-11.00,and the content is between 2.42%-2.50%,which meets the quality control requirements.The stability of the injection was investigated.Under light conditions,itsappearance color was deepened and its content decreased by about 0.15%,indicating that the injection was unstable under light conditions.At 60℃,its appearance color deepened and its content decreased by about 0.2%,indicating that the injection was unstable at 60℃.The results of the accelerated test showed that the color,clarity,pH and physicochemical properties of the drug were stable under the condition of 30℃and 65%relative humidity.The safety of the injection was investigated.The sarafloxacin injection had no obvious irritation in the rabbit skin irritation test;it had no obvious irritation to the muscles in the muscle irritation test;it had no hemolysis,indicating that the injection was relatively safe.The sample was pretreated with C18 solid phase extraction column,and the content of sarafloxacin in plasma was determined by HPLC fluorescence method.The detection results showed a good linear relationship within the range of 0.05-3.2 g/mL,with R2 of 0.9996;The RSD values of the intra-day precision and the inter-day precision of sarafloxacin are both less than 10%;the recovery rate is between 95.26%and 113.06%,and the RSD is 7.39%;the method specificity,precision and accuracy are good.Intramuscular injection of 10mg/kg was given to rats,the DAS2.0 software was used for fitting analysis,and the results showed that the best pharmacokinetic model of sarafloxacin potassium injection in rats was the first-level absorption two-compartment model,pharmacokinetic parameters:t1/2αis 0.875±0.131h,t1/2βis4.898±0.733h,t1/2Kais 0.494±0.046h,AUC（0-t）is 2.466±0.016mg/L*h,AUC（0-∞）is2.826±0.073mg/L*h,Tmaxis 1.03±0.02h,Cmaxis 0.479±0.007mg/L.Compared with the commercially available sarafloxacin hydrochloride injection,the absorption of sarafloxacin potassium injection in rats is relatively slow,and the effective blood concentration is maintained for a longer time. |
