It is necessary to select a suitable solvent to completely dissolve the sample to be tested. Azithromycin is almost insoluble in water to ensure complete release of residual acetone in the sample. Soluble in methanol, absolute ethanol, dilute hydrochloric acid. In this experiment, the headspace method was used, and the temperature of the sample was measured at 80 °C for 45 minutes with water as the solvent. The sample of the sample in the sample was determined by n=6 batch number. The result was significantly lower, indicating that the sample was hot. The solubility in water is also extremely small and cannot be determined by using water as a solvent. The solvent specified in the Pharmacopoeia is benzene, benzene is a carcinogenic organic solvent, and should be prevented as much as possible; using methanol or absolute ethanol as solvent, the peak time is higher than the acetone to be tested. Early and too close to the acetone peak, it will interfere with the detection of acetone and will not be considered; the use of dilute hydrochloric acid will affect the service life of the capillary column, and it will not be used. According to the ICH guidelines and literature on solvent residues in pharmaceuticals, this paper The choice of DMF as a solvent has a satisfactory result. The test is also applicable to the examination of residual acetone in the DMF antibiotic bulk drug which is insoluble in water, provided that the raw material has used acetone as an extraction solvent in the refining process.
Hydrogen flame ionization detector (FID with NN dimethylformamide (DMF as solvent, abstract: purpose to establish a method for determination of acetone residue in azithromycin. The method uses capillary gas chromatography . Elastic quartz capillary column DB62430m053mm3μm column temperature 40 °C maintenance 10min to 40 ° C / min rate to 200 ° C, maintain 10min carrier gas: high purity nitrogen, line speed 4ml / min hydrogen: 40ml / min inlet temperature 250 ° C; detection port temperature 280 ° C; air 400ml / min tail blowing The 25ml/min split ratio of 2:1 injection volume 1μl results in a recovery rate of 9984% RSD of 087%. Conclusion This method is simple, sensitive, exclusive, accurate and less toxic.
Key words: capillary gas chromatography; azithromycin; acetone; residual solvent
Acetone may remain in the preparation process, and azithromycin is a new generation of macrolide antibiotics. The Chinese Pharmacopoeia 2000 edition stipulates that azithromycin should be tested for residual acetone. The Pharmacopoeia stipulates that benzene is used as a solvent, but benzene is a type of solvent specified by ICH. It is highly toxic and carcinogenic and should be prevented from being used. In this paper, capillary gas chromatography, hydrogen flame ionization detector (FID with NN dimethylformamide (DMF as solvent, elastic quartz capillary column DB62430m053mm3μm for the determination of the residual amount of acetone), the results indicate that the method is simple, Sensitive, exclusive, accurate, and low toxicity, it can completely replace the 2000 version of the Chinese Pharmacopoeia for the determination of acetone residues in azithromycin.
1 instruments and reagents
6890N gas chromatograph (Agilent) hydrogen flame ionization detector (FID azithromycin bulk drug (lot number 040229040333040415 provided by Ningbo Asia Pacific Pharmaceutical Co., Ltd.; acetone, DMF and other organic solvents are analytically pure.
2 chromatographic conditions
The carrier gas was maintained as high-purity nitrogen gas for 10 minutes, and the column was an elastic quartz capillary column DB62430m053mm3μm. The column temperature was maintained at 40 ° C for 10 min and the temperature was raised to 200 ° C at a rate of 40 ° C / min. Line speed 4ml/min hydrogen 40ml/min inlet temperature 250°C; detection port temperature 280°C; air 400ml/min tail blowing 25ml/min split ratio 2:1 injection volume: 1μl
3 methods and results
Make up with DMF. The standard solution was taken to a standard storage solution of 010203040 and 50 ml in a 200 ml volumetric flask and made up to volume with DMF. The sample solution accurately weighed the sample 0400g in a 10ml volumetric flask. The preparation solution of the 3.1 solution was accurately weighed into acetone 102g in a 100ml volumetric flask. Dissolve and dilute with DMF.
The peak area of ​​the acetone peak was measured to regress the acetone concentration. The preparation of the 3.2 gauge curve and the results were taken from the above series of standard solutions. Get the regression equation as y=44241x+15818r=09993
The measured detection limit of acetone zui was 2 μg S/N = 3 3.3 The detection limit was under the above chromatographic conditions.
The recovery rate of the sample was 9984% RSD was 087% n=6 3.4 Precision and recovery The precision and recovery test of the method was tested.
4 discussion
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