Establishment of national reference standard of tazobactam impurity A / 中国药科大学学报

@#To improve the standard of quality control of tazobactam and its preparations in China, national reference standard of tazobactam impurity A was developed. After tazobactam impurity A was synthesized, its structure was validated by infrared (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR), and its content uniformity and short-term stability were measured and investigated. Then, water content and residue on ignition of impurity A were determined, and its purity was determined using high performance liquid chromatography (HPLC) with 10 mmol/L ammonium acetate solution-acetonitrile (98∶2) as the mobile phase. Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance. Meanwhile, nuclear magnetic quantitative method was used to calculate the content, which was mutually verified with the mass balance method. The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41. Within the 95% confidence range, the ratio of inter- and intra-bottle variance of impurity A after separation was 0.61 (< F0.05(11,12)), proving that the uniformity was satisfying. The contents of organic impurity, water content and inorganic impurity in impurity A were 0.90%, 1.24% and 0.25%, respectively. The content of impurity A was determined to be 97.6% by mass balance method, which was basically consistent with the result of nuclear magnetic quantitative method (97.1%). Under the condition of 25 °C, the area normalized purity of impurity A was 99.1% at 0, 3, 5 and 10 days, proving that the sample was stable at room temperature for 10 days. Finally the first batch of national standard substance of tazobactam impurity A was established successfully.

Establishment of National Reference Standards of Sulfadimidine Impurities / 中国药学杂志

OBJECTIVE: To establish the national reference standards of sulfadimidine impurities thus to provide guarantee for improving the standard of quality control of sulfadiazine in China. METHODS: First, the structures of sulfadimidine impurities A and E were validated by infrared spectrocopy, mass spectrum and nuclear magnetic resonance method. Then, the purities of impurities A and E were determined using the method of related substance test for sulphadiazine in the European Pharmacopoeia (version 9.0),their water content and residue on ignition were determined as well. The contents of sulfadimidine impurities A and E were determined by using mass balance method. Meanwhile, external standard method and nuclear magnetic quantitative method were used to calculate the content, which were mutually verified with the mass balance method. Finally, the correction factors of sulfadiazine impurities A and E at 241 nm were determined using standard curve method. RESULTS: The structures of sulfadimidine impurities A and E were confirmed, and the contents of impurities A and E were 99.1% and 98.7%, respectively, which were calculated by mass balance method. The results were consistent with those obtained from external standard method and nuclear magnetic quantification method. The correction factors of impurities A and E to sulfadimidine were 0.97 and 0.63, respectively. CONCLUSION: The first batch of national standard substances of sulfadimidine impurities A and E were established successfully.

Study on Micronization Technology of Alitretinoin Crude Drug / 中国药房

OBJECTIVE:To screen the optimal micronization technology of Alitretinoin crude drug. METHODS:Using characteristic value of particle size distribution [d(0.9)] and the content of impurity A of crude drug after crushed as indexes, crushing method(universal pulverizer,ball crusher,airslide disintegrating mill),crushing gas source(compressed air,high pressure nitrogen)and crushing pressure(0.2,0.4,0.6 MPa)of Alitretinoin crude drug were screened,and validation test was also conducted. RESULTS:The optimal technology was as follows as airslide disintegrating mill,high pressure nitrogen as gas source,at 0.4 MPa.In validation test,particle sizes for 3 batches of crude drug after crushed were 8.57,8.55,8.54 μm(<10 μm, RSD=0.15%,n=3). The content of impurity A was not increased compared with before crushed(0.07%). CONCLUSIONS:Screened micronization technology of Alitretinoin crude drug is feasible and stable in quality.

Determination of Related Substances in Methylphenidate Hydrochloride for Injection by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in Methylphenidate hydrochloride for injection. METHODS:HPLC method was adopted. The determination was performed on Waters symmetry C18 column with mo-bile phase consisted of methanol-0.01 mol/L potassium dihydrogen phosphate solution(60:40,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm,the column temperature was 35 ℃ and sample size was 10 μL. RESULTS:The linear range of impurity A and B were 0.02-3.0 μg/mL(r=0.9998). The limits of quantitation were 0.2,0.6 ng,and the limits of detec-tion were 0.06,0.2 ng,respectively. RSDs of precision,stability and reproducibility were all lower than 2.0%;recoveries were 98.2%-100.0%(RSD=0.56%,n=9),98.0%-100.3%(RSD=0.70%,n=9),respectively. CONCLUSIONS:The method is sim-ple,accurate and suitable for the determination of related substance in Methylphenidate hydrochloride for injection.

Determination of Related Substances in Norfloxacin Glutamate and Sodium Chloride Injections / 中国药师

Objective:To detect the related substances in norfloxacin glutamate and sodium chloride injections on the basis of nor-floxacin related substances analysis method described in Chinese Pharmacopoeia 2010 edition to establish a more scientific and feasible method. Methods:HPLC was performed under the following conditions:a Diamonsil C18(2)(250 mm ×4.6 mm,5μm) column, mo-bile phase A of 0. 025 mol·L-1 phosphoric acid-acetonitrile(87∶13), phase B of acetonitrile, with gradient elution at a flow rate of 1. 0 ml·min-1 , the detection wavelength of 278nm and 262nm, the injection volume of 20 μl, and the column temperature of 25℃. Results:Under the HPLC conditions, the samples had good stability and separation. An excellent linear relationship was achieved within the range of 0. 032-3. 179μg·ml-1(r=1. 000 0),the detection limit of impurity A was 0. 159 ng,and the average recovery was 98. 3% with RSD of 0. 64%(n=9). Conclusion:Compared with the existing methods, the gradient elution method is accurate, sen-sitive, specific and reproducible, and can be used in the determination of related substances in norfloxacin glutamate and sodium chlo-ride injections.

Determination of related substances in lapatinib ditosylate tablets by HPLC / 中国药学杂志

OBJECTIVE: To establish a determination method of the related substances of lapatinib ditosylate tablets by HPLC. METHODS: Waters Xterra MS C18 column (4.6 mm × 250 mm, 5 μm) was selected; 0.01 mol · L-1 sodium dihydrogen phosphate solution (pH adjusted to 3.2 with phosphoric acid) was mobile phase A, acetonitrile was mobile phase B, and gradient elution was used at a flow rate of 1.0 mL · min-1. The detection wavelength was set at 265 nm, and the column temperature was 40°C. RESULTS: Lapatinib Impurity A, LAPA-2 and LAPA-1 had good linearity in the range of 0.02-8.08, 0.02-8.26 and 0.02-8.29 mg · mL-1, respectively (r≥0.9999). The limits of quantitation (LOQ) were 1.0, 1.4, and 2.1 ng, respectively. The average recovery (n=9) was in the range of 100.2%-102.9%, and RSDs (n=9) were in the range of 0.02%-0.66%. CONCLUSION: The method is simple, accurate, and specific and can quantitatively determine the related substances of lapatinib ditosylate tablets.