| Objective:In this paper,for the first time in the establishment of its quality standards for a systematic and complete research of Olanzapine.The study provides the foundation for controlling the product quality better.Methods:A simple method was developed by HPLC method about material inspection.The detected wavelength,test conditions,column,mobile phase system and proportion were optimized to establish the method and the optimum conditions were established.HPLC system:Waters 2695 HPLC,with PDA photodiode array detector;using the column of DIKMA Inertsil C8-3(4.6 mm×250 mm 5 ?m),The buffer was:13 g dodecyl sodium sulfate was dissolved in 1500 mL of water,add 5 mL phosphate,with a saturated aqueous solution of sodium hydroxide to adjust the pH=2.5;mobile phase A buffer:acetonitrile=52:48;mobile phase B was acetonitrile:buffer=70:30;detection wavelength was 220 nm;column temperature was 35?;flow rate of 1.5 mL/min;injection volume was 20 ?L.A sample method was developed by GC for the determination of residual organic solvents in Olanzapine.The GC system was Agilent Technologies 6890N gas chromatographic system and Agilent 7694E headspace injector.It was achieved by the column of DB-624(30.0 m×0.53 mm×3.00 ?m)(6%-propyl cyanide benzene-94%-dimethylsiloxane copolymer),the initial temperature was 50? and maintenance for 2 minutes,then the temperature raise up to 200? at heating rate of 10?/min,and maintenance for 2 minutes.FID temperature:250?;carrier gas:Nitrogen;constant pressure:3.0 psi;the headspace temperature:80?;balance time:25 minute;injection volume:3.0 mL.The stress tests of Olanzapine were studied in the case of direct exposure.Using simulation packaging stuff of drugs,tested by accelerated tests for 6 months and the long-term test for 12 months.Results:The HPLC method about material inspection indicates that the sample could be separated goodly with the intermediates and related materials by contrast test of intermediates and destructive test of the sample.The results showed that the method was accurate and rapid,which appeared to has a good linearity with regression equation(A=3260606.098C-4067.128 r=0.9996).The result of the determination of residual organic solvents in Olanzapine indicates that seven solvents(methanol,ethanol,isopropanol,dichloromethane,tetrahydrofuran,n-heptane and chlorobenzene)showed good linearity in a detected concentration range,regression equation:A=-11.315+864.484C,r=0.9998;A=9.487+1137.387C,r=0.9995;A=19.200+1430.406C,r=0.9994;A=3.978+1536.811C,r=0.9994;A=12.803+7330.585C,r=0.9991;A=295.719+66545.244C,r=0.9980;A=1.246+1524.163C,r=0.9995;and good repeatabilities were RSD:3.09%?1.83%?1.75%?1.73%?1.78%?1.98%?1.89%;The Olanzapine rage recovery:108.37%,104.02%,102.80%102.09%,94.11%,90.44%,97.52%.The results showed there were no methanol,ethanol,dichloromethane and tetrahydrofuran in Olanzapine and the residual isopropanol,n-heptane and chlorobenzene was lower than its limits standard.In the meanwhile,a simple method was developed by HPLC,which is rapid,efficient and save apis,environmental protection.The reproducible RSD was 0.50%.The contents of 6 batches of samples were not low than 99.0%.The result of the stability tests of Olanzapine indicates that the sample was stable with strong light,high temperature and high humidity;and its appearance,content,weight and the related materials were no transform.Conclusions:After the above a series of test,according to China pharmacopoeia of new drug quality requirements,formulated the new drug Olanzapine quality standard draft,enhanced the quality controllability of the product in clinical application research. |
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