Study On The Hepatotoxicity Of Sodium Foscarnet And Its Compatibility With Oxymatrine

Objective To establish an HPLC method for the determination of foscarnet sodium injection and its related substance.To study the effect of foscarnet sodium on liver and kidney function and related parameters in rats.To investigate the compatibility of foscarnet sodium chloride injection and oxymatrine injection at 4?,23±2?and 45?.Method Krosimol C₁₈?150×4.6mm,5?m?)was used with the mobile phase of Methanol-40mM phosphate buffer?containing 0.25 mmol·mL^-11 tetrahexyl ammonium hydrogen sulfate,pH 7.6??v/v,25/75?;The flow rate was 1.0 mL·min^-1,and the detection wavelength was 230nm at the 30??Forty Sprague-Dawley rats were randomly divided into 4 groups:the rats in the low,medium and high dose groups(300 mg·kg^-1,600 mg·kg^-1,900 mg·kg^-1)were injected intraperitoneally,while the control group were injected with equal volume of normal saline.The rats were given once a day for 2 weeks.The urine samples were collected within 24 hours.The contents of creatinine?CR?and urinary protein?U-TP?were measured and the corresponding CCr values??were calculated.?ALT?,aspartate aminotransferase?AST?,alkaline phosphatase?ALP?,urea?UREA?,creatinine?CR?and triglyceride?TG?The organ coefficients were measured,and then one lobe liver and the kidney embedded in the same side were taken respectively.The tissue structure was observed under a light microscope after HE staining.The initial solutions was prepared according to the clinical dose of foscarnet sodium and oxymatrine injection,and stored at 4?,23±2?and 45?.The solutions were inspected for changes in pH and the visual inspection such as the precipitation,cloudiness,and discoloration at each sampling interval?0?8?12?24?48?72?96?120?168?240?360 h?.Samples were taken at 0,2,4,8,24,48,72,96,120,168,240,360 h to check the sample content changes by high performance liquid chromatography?HPLC?.Results The linear range of the method was 5⁸00?g·mL^-1?R²=0.9991?,with RSD of was0.35%?n=5?,and the averge recovery was 99.97%,with RSD of was 0.83%.The content of phosphate and phosphite was in line with the provisions.Compared with the control group,the body weight growth rate decreased and the organ coefficient increased?P<0.05?.The renal coefficient increased in a dose-dependent manner.The contents of ALT,AST,ALP,Uera,Cr and TG in plasma increased?P<0.05?,while the contents of Cr and CCr in urine decreased?P<0.05?in a dose-dependent manner.high.Under the conditions of 4?,23±2? and 45?for 15 days,the liquid of foscaminin and oxymatrine was clarified,no precipitation,not muddy,no clouds,no bubbles,no discoloration and the change of pH remained stable.Conclusion The method is rapid,accurate for the determination of foscarnet sodium injection and its related substance.The continuous use of high-dose foscarnet has a damaging effect on the liver and kidney,and the damage to the kidneys is more serious.The severity is related to the dose..The stability of foscarnet sodium chloride injection and oxymatrine injection in vitro is good,and the compatibility solution was stable for at least 15 days.