Determination of residual organic solvents in Apixaban bulks drug by headspace gas chromatography / 药物评价研究

Objective To establish a method for determination of the twelve residual organic solvents,including methanol,ethanol,acetone,isopropanol,tert-Butyl methyl ether,dichloromethane,aceticether,tetrahydrofuran,triethylamine,trimethylorthofor-Mate,morpholine,N,N-Dimethylformamide in Apixaban bulks drug.Methods Gas head-space chromatography was applied to this study.The column was DB-624 silica capillary column (30.0 m × 0.53 mm × 3.00 μm) and the carrier gas was high purity nitrogen;The vial temperature was 100 ℃,and the vial time was 20 min.The Column temperature was kept at 40 ℃ for 6 min,then the temperature was raised to 220 ℃ at the rate of 20 ℃/min and subsequently sustained for 10 min.FID detector temperature and injection temperature were both 250 ℃.The N2 flow rate was 2.8 mL/min.Split ratio was 5∶1.Results Twelve kinds of solvents were completely separated and determined with a good linearity (r =0.9994-0.9999).The RSD values of precision experiments and the average recovery was in line with the requirements.Conclusion Theanalytical method is simple,accurate and sensitive,which could be used for determination of residual organic solvents in Apixaban bulks drug.

Determination of Residual Organic Solvents in Imported Lidocaine Patches by GC / 中国药师

Objective:To establish a GC method for the determination of residual organic solvents in lidocaine patches. Methods:GC was carried out on a DB-WAX capillary column (30 m × 0. 25 mm, 0. 5 μm). The detector was FID and the carrier gas was He. The initial temperature was 50℃, maintained for 8 min, and then raised to 250℃ with a rate of 50℃ per min. The inlet temperature and the detector temperature were 280℃. The separation was 50 ∶1. Results:The linear range of acetone, ethyl acetate and methanol was 15. 0-600. 0 μg·ml-1. The average recovery was 97. 4% (RSD =3. 2%, n=9), 95. 6% (RSD=1. 9%, n=9) and 112. 0%(RSD =4. 5%, n=9), respectively. Conclusion:The method is simple and accurate,which can be used for the determination of re-sidual organic solvents in lidocaine patches.

Determination of Residual Organic Solvents in Erlotinib Hydrochloride by Headspace Gas Chromatography / 中国药师

Objective:To establish a headspace capillary gas chromatography method for the determination of residual solvents in erlotinib hydrochloride .Methods:A DB-624 capillary column (30 m ×0.53 mm, 3.0 μm) was used and the carrier gas was nitro-gen.The flow rate was 2.0 ml· min-1 and the inlet temperature was 190℃.The FID detector temperature was 230 ℃.The column temperature program was with the initial temperature of 35℃( maitaining 8 min) , risen to 170℃with the rate of 28℃· min-1 ( main-taining 8 min) , and then risen to 200℃with the rate of 32℃· min-1 ( maintaining 7 min) .The headspace vial temperature was 100℃and the time was 30 min.Results:Ethanol, isopropanol, methylene chloride and n-butanol had a good linear relationship within the range of 0.68-409.14 μg· ml-1 (r=0.999 8),0.67-404.88 μg· ml-1 (r=0.999 8),1.71-51.31μg· ml-1 (r=0.999 7) and 0.72-431.12 μg· ml-1(r=0.999 8), respectively.The average recovery was 99.0% (RSD=0.41%, n=9), 100.2%(RSD=0.52%, n=9),97.1%(RSD=1.75%, n =9) and 102.5% (RSD=1.08%, n=9), respectively.Conclusion: The method is simple and accurate , which can be used for the determination of four residual organic solvents in erlotinib hydrochloride .

Determination of Residual Organic Solvents in Dimemorfan Phosphate by GC / 中国药师

Objective:To determine the content of chloroform, ethyl acetate and DMF in dimemorfan phosphate by gas chromatog-raphy (GC). Methods:The capillary gas chromatography was used with a PEG-20M column, programmed temperature, water as the solvent and FID as the detector. Results:The three organic solvents were separated and showed good linear relationship (r>0. 999 0). The detection limit of chloroform, ethyl acetate and DMF was 0. 63,0. 60 and 8. 92μg·ml-1 , respectively. The residues of the organ-ic solvents in three batches of the samples all met with the requirements of ICH. Conclusion: The method is sensitive, accurate and reliable, and can be used in the quality control of dimemorfan phosphate.

Determination of Organic Solvent Residues in Testosterone Cypionate / 医药导报

Objective To establish a headspace GC method for the determination of residual organic solvents in testosterone cypionate. Methods The residual organic solvents were determined by GC with DB-WAX capillary colum(30 m× 0. 32 mm,0. 25 μm)and FID detector at 230℃,using high purity nitrogen as the carrier gas by headspace sampling. The flow rate was 1. 5 mL·min-1 ,the split ratio was 20:1,the temperature of injection port was 220℃,the headspace heating temperature was 70 ℃,and the headspace balance time was 40 mins. The content of residues was calculated by using n-propanol as the internal standard. Results Four residual solvents were completely separated. There were good linearity for m-ethanol,ethanol,benzene and pyridinein in the ranges of 4. 17-2. 50×103 μg·g-1(R=0. 999 9),4. 18-2. 51×103 μg·g-1(r=0. 999 6),0. 84-172 μg·g-1 (r=0. 998 1),and 2. 95-1. 77×103μg·g-1(r=0. 999 9),respectively. The detection limit was 2.08,1. 23,0.28,and 0. 87 μg·g-1,respectively. The average recovery of methanol,ethanol,benzene and pyridinein was 102. 2%(RSD=4. 0%),99. 6%(RSD=1. 9%),112. 6(RSD=5. 6%),and 98. 9%(RSD=1. 6%),respectively. Conclusion This method is reliable,sensitive, accurate and can be used for the determination of residual organic solvents in testosterone cypionate.

Determination of Residual Organic Solvents in Flupirtine Maleate by Headspace Gas Chromatography / 中国药师

Objective:To determine the content of methanol, alcohol and isopropanol in flupirtine maleat by headspace gas chro-matography. Methods:The capillary gas chromatography with programming temperature was established with an FID detector and a DB-624(30 m × 0. 53 mm,3. 0 μm) capillary column. The temperature of the injector and the detector was 200℃ and 250℃, respec-tively. The residual organic solvents were determined by an external standard method. Results: Methanol, alcohol and isopropanol showed good linearity within the range of 2. 182~152. 74(r=0. 999 1), 3. 546-248. 22(r=0. 9998)and 4. 082-285. 74 μg·ml-1(r=0. 999 7) with the average recovery of 97. 7%(RSD=1. 5%),99. 0%(RSD=1. 1%)and 98. 8%(RSD=1. 1%)(n=5), respec-tively. Conclusion:The method is simple, sensitive and accurate, and can be used in the residual solvents detection for flupirtine mal-eat.

Determination of Residual Toluene in Diclofenac Sodium Raw Material by GC / 中国药师

Objective:To establish a detection method for residual toluene in diclofenac sodium raw material by GC. Methods:An HP-5 column (0. 53 mm × 30 m, 2. 65 μm) with nitrogen as the carrier gas was employed for the separation. The temperature of the column, injection port and FID detector was set at 50℃, 200℃ and 250℃, respectively. An internal standard method with isooctane as the internal standard was used to assay the residual amount after the sample was dissolved in DMSO. Results:The linear calibration curve was obtained over the range of 9. 27-111. 19μg·ml-1(r=0. 999 4). The mean recovery was 97. 27%(RSD=2. 80%,n=9). The LOD and LOQ was 0. 59μg·ml-1 and 1. 46μg·ml-1 , respectively. The residual contents of toluene in 3 batches of the products all met the relevant regulations. Conclusion:The established method is reliable and accurate, and can be used in the quality control of diclofenac sodium.

Determination of Residual Organic Solvents in Paclitaxel by Capillary GC / 中国药师

Objective:To establish a capillary GC method for the determination of residual organic solvents in paclitaxel. Meth-ods:The standard solution and test solution was respectively injected into an HP-INNOWAX sillica capillary column by headspace in-jection. The chromatograms were recorded with an FID. The injection port and detector temperature was 250℃ and 300℃, respective-ly, the initial column temperature was kept at 35℃ for 5 min, and then was risen to 260℃ at the rate of 25℃/min. Results:The four residual organic solvents could be separated completely. The resolution and sensitivity were acceptable. Conclusion: The method is proved to be simple, rapid, sensitive and reliable, and can be used in the determination of residual organic solvents in paclitaxel.

Determination of Residual Organic Solvents in Letrozole by Headspace Capillary Gas Chromatography / 中国药房

OBJECTIVE: To establish headspace capillary gas chromatography for the content determination of residual solvents in letrozole, such as chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol. METHODS: Dissolved in dimethyl sulfoxide, chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol in letrozole were determined by headspace gas chromatography with HP-5 capillary gas chromatography. ECD was applied for chloroform, while FID was applied for the other residual solvents. RESULTS: The liner ranges of chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol were 1.028～10.28 mg?L-1(r=0.999 9), 94.68～946.8 mg?L-1 (r=0.999 7), 94.64～946.4 mg?L-1(r=0.999 7), 110.64～1 106.4 mg?L-1(r=0.999 7), 15.12～151.2 mg?L-1(r=0.999 6), 116.48～1 164.8 mg?L-1(r=0.999 5), respectively. The average recoveries of the residual organic solvents ranged from 97% to 102%. The detection limits were 20～90 ?g?L-1. The residual levels of the six organic solvents in three batches of samples were all up to the standard stipulated in Chinese Pharmacopeia. CONCLUSIONS: The method is simple, sensitive, accurate and reliable for the content determination of residual organic solvents in letrozole.