ANALYTICAL REPORT- PENTOBARBITAL - Sedation - home：分析报告-戊巴比妥钠镇静-首页.doc

ANALYTICAL REPORT- PENTOBARBITALIntroduction- To explore the stability of diluted pentobarbital solution in D5W at room temperature and humidity.Figure 1 Pentobarbital Chemical Structure - Note:The alkyl tail is the potential site of instability for this drug.Supplies: Nembutol Sodium Solution 20mg/ml 20ml vial Ovation Pharmaceuticals Inc Lot 562453F Exp Sept 2010 Pentobarbital sodium injection contains the following ingredients Each milliliter of solution contains:Pentobarbital Sodium50mgPropylene Glycol40%(v/v)Alcohol10%Hydrochloric and/or Sodium HydroxideAdjust pHWater for injectionQS D5W Injection 1000 ml Viaflex bag Baxter Healthcare Lot C772590 Exp 10/2010Procedure: (a) To make a 10mg/ml solution of a 50mg/ml solution use a 1:5 dilution or 1ml into 5 mls of TOTAL solution. (b) To make a 20mg/ml solution of a 50mg/ml solution use a 2:5 dilution or 2mls into 5 mls of TOTAL solution. Dilute 1/100 to be able to perform the UV Remove at various intervals and observe the decline in concentration.REFERENCE DATA:STABILITY- (Trissels 15th Edition) “Aqueous solution of pentobarbital are not stable.The commercially available pentobarbital sodium in a propylene glycol vehicle is more stable.In acidic media, pentobarbital may precipitate. No solution containing a precipitate or that is cloudy should be used.”Syringes: (Trissels 15th Edition): “Undiluted pentobarbital (Abbott) 50mg/ml was packaged in 1ml glass and Polypropylene syringes and 3ml polypropylene syringes (Becton- Dickinson) and stored at 25C. NO pentobarbital sodium loss by HPLC analysis occurred in 31 days.EXPERIMENTAL RESULTS:Figure 2 UV scan of Pentobarbital 50mg/ml diluted 1/100 in Sterile Water.The UV scan of pentobarbital is seen in figure 2. Pentobarbital exhibits a peak at 240nm which can be used as the measured.Solutions were made at 20 mg/ml and 10mg/ml in dextrose 5% water and were measured at 15 minute intervals.The results reported were the calculated concentrations using the injection (50mg/ml) diluted 1/100 as thestandard. The results for each analysis were determined in duplicate. Table 1 summarizes the results for theroom temperature stability of pentobarbital. Figure 3 illustrates the stability of Pentobarbital at 10 and 20 mg/mlconcentrations of the diluted injection in D5W. Table I Analytical Results for the pentobarbital analysis ABCMeanSD.RSD20mg/ml0hr17.94618.10918.64618.5518.4818.34620.30241.64815min18.64818.61718.60518.5918.61500.02460.13230min17.67717.67417.63917.64417.63317.65340.02060.117After 30 minutes a precipitate was observed10mg/ml0hr8.71798.68388.67828.67648.59888.671020.04380.50515min8.33868.33728.30918.29618.320250.02110.25330min7.71267.72077.7167.72127.85067.81617.744220.05960.769After 30 minutes the solution became cloudy Figure 3- Graphical results of the stability of pentobarbital solutions at 10 and 20 mg/ml.Figure 1Using a simple linear regressions (Y=MX + B)Calculating the 80% value of the concentration of drug yields the following information:SlopesY intercepts20%Y=mx+bValue20mg/ml-1.385218.551114.842.7hrs10mg/ml-1.85368.70866.86680.9936hrFINAL SUMMARY.Pentobarbital is very unstable in aqueous media especially when put in a pH of less than 9.The pH of this injection is between 9.8 and 11.0 (USP). After dilution in d5w both concentrations precipitated out after 30 minutes at room temperature. Calculating the value at 80% concentration yielded 2.7 hours and 0.9936 hourshowever in both cases the UV determination was not reliable (precipitation) after 30 minutes.Dilution of Pentobarbital can only