高效液相色谱法测定头孢地尼薄膜衣片中的特定杂质
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摘要
目的采用高效液相色谱法测定头孢地尼薄膜衣片中杂质A和杂质B的含量。方法采用Kromasil 100-5-C_(18)(4.6 mm×250 mm,5μm)色谱柱,以0.25%四甲基氢氧化铵水溶液(用磷酸调pH至5.5),每1000 mL中加入0.1 mol·L~(-1)乙二胺四乙酸二钠水溶液0.4 mL为流动相A;0.25%四甲基氢氧化铵水溶液(用磷酸调pH至5.5)-乙腈-甲醇(500∶300∶200),每1000 mL中加入0.1 mol·L~(-1)乙二胺四乙酸二钠水溶液0.4 mL为流动相B;按照梯度:0～2 min 5%B,25～42 min 25%～50%B,42～43 min 50%～5%B,43～60 min 5%B进行洗脱。柱温为40℃,流速为1 mL·min~(-1),检测波长为254 nm,进样量为20μL。结果头孢地尼与其降解产物分离度良好。杂质A和杂质B分别在2.10～21.0μg·m L~(-1)和0.121～6.06μg·m L~(-1)与峰面积线性关系良好,线性方程分别为Y=2.147×10~4X-4.507×10~3(r=0.9999,n=7)和Y=2.954×10~4X-473.77(r=0.9999,n=7)。杂质A和杂质B的回收率范围分别为110.86%～118.48%和98.00%～102.33%。结论该方法准确度、灵敏度、耐用性良好,可用于头孢地尼薄膜衣片中杂质A和杂质B的定量测定。
Objective To determine the content of impurity A and impurity B in cefdinir film-coated tablets by HPLC. Methods A Kromasil 100-5-C_(18)(4.6 mm×250 mm, 5 μm) column was adopted for the chromatographic separation. The mobile phases consisted of A [0.4 mL 0.1 mol·L~(-1) EDTA-2 Na adding in every 1000 mL 0.25% tetramethylammonium hydroxide(pH adjusting to 5.5 with phosphoric acid)] and B [0.4 mL 0.1 mol·L~(-1) EDTA-2 Na adding in every 1000 mL 0.25% tetramethylammonium hydroxide(pH adjusting to 5.5 with phosphoric acid)-acetonitrile-methanol(500∶300∶200)]. The gradient program included 0-2 min, 5% B; 25-42 min, 25% B-50% B; 42-43 min, 50% B-5% B; 43-60 min, 5% B. The column temperature was 40 ℃, the flow rate was 1 mL·min~(-1), the detection wavelength was 254 nm and the injection volume 20 μL. Results Cefdinir and degradation products were well separated. Good linearity for impurity A and impurity B were respectively obtained at 2.10-21.0 μg·mL~(-1) and 0.121-6.06 μg·mL~(-1), and the linear equations of impurity A and impurity B were Y = 2.147×10~4 X-4.507×10~3(r = 0.9999, n = 7) and Y= 2.954×10~4 X-473.77(r = 0.9999, n = 7). The recoveries of impurity A and impurity B were 110.86%-118.48% and 98.0%-102.3%, respectively. Conclusion The method is accurate, sensitive, and durable for the determination of impurity A and impurity B in cefdinir film-coated tablets.
Objective To determine the content of impurity A and impurity B in cefdinir film-coated tablets by HPLC. Methods A Kromasil 100-5-C_(18)(4.6 mm×250 mm, 5 μm) column was adopted for the chromatographic separation. The mobile phases consisted of A [0.4 mL 0.1 mol·L~(-1) EDTA-2 Na adding in every 1000 mL 0.25% tetramethylammonium hydroxide(pH adjusting to 5.5 with phosphoric acid)] and B [0.4 mL 0.1 mol·L~(-1) EDTA-2 Na adding in every 1000 mL 0.25% tetramethylammonium hydroxide(pH adjusting to 5.5 with phosphoric acid)-acetonitrile-methanol(500∶300∶200)]. The gradient program included 0-2 min, 5% B; 25-42 min, 25% B-50% B; 42-43 min, 50% B-5% B; 43-60 min, 5% B. The column temperature was 40 ℃, the flow rate was 1 mL·min~(-1), the detection wavelength was 254 nm and the injection volume 20 μL. Results Cefdinir and degradation products were well separated. Good linearity for impurity A and impurity B were respectively obtained at 2.10-21.0 μg·mL~(-1) and 0.121-6.06 μg·mL~(-1), and the linear equations of impurity A and impurity B were Y = 2.147×10~4 X-4.507×10~3(r = 0.9999, n = 7) and Y= 2.954×10~4 X-473.77(r = 0.9999, n = 7). The recoveries of impurity A and impurity B were 110.86%-118.48% and 98.0%-102.3%, respectively. Conclusion The method is accurate, sensitive, and durable for the determination of impurity A and impurity B in cefdinir film-coated tablets.
引文
[1]刘国洪.头孢地尼分散片的研究[D].广州:广州中医药大学,2011.
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[8]蒋煜,张哲峰,王虹.β-内酰胺类抗生素异构体杂质研究和质控进展[J].中国抗生素杂志,2010,35(8):561-566.
[9]胡昌勤,蒋煜,张靖溥,等.对β-内酰胺抗生素中微量不稳定杂质研究策略与方法的思考[J].中国新药杂志,2013,22(1):4-12.
[10]中国药典2015年版.二部[S].2015:244-249.
[11]Llinás A,Vilanova B,Frau J,et al.Chemical reactivity of penicillins and cephalosporins.intramolecular involvement of the acyl-amido side chain[J].J Org Chem,1998,63(24):9052-9060.
[12]Okamoto Y,Kiriyama K,Namiki Y,et al.Degradation kinetics and isomerization of cefdinir,a new oral cephalosporin,in aqueous solution.1[J].J Pharm Sci,1996,85(9):976-983.
[13]Okamoto Y,Kiriyama K,Namiki Y,et al.Degradation kinetics and isomerization of cefdinir,a new oral cephalosporin,in aqueous solution.2.Hydrolytic degradation pathway and mechanism forβ-lactam ring opened lactones[J].JPharm Sci,1996,85(9):984-989.
[14]Indelicato JM,Norvilas TT,Pfeiffer RR,et al.Substituent effects upon the base hydrolysis of penicillins and cephalosporins.Competitive intramolecular nucleophilic amino attack in cephalosporins[J].J Med Chem,1974,17(5):523-527.
[2]Chatterjee A,Moland ES,Thomson KS.Cefdinir:An oral alternative to parenteral cephems[J].Diagn Microbiol Infect Dis,2005,51(4):259-264.
[3]Guay DRP.Cefdinir:An advanced-generation,broadspectrum oral Cephalosporin[J].Clin Ther,2002,24(4):473-489.
[4]周利胜,曹银生,贺松坡.穿王消炎片联合头孢地尼治疗慢性咽炎的临床研究[J].现代药物与临床,2018,33(11):147-150.
[5]Takaya T,Takasugi H,Masugi T,et al.7-substituted-3-vinyl-3-cephem compounds and processes for production of the same:US,4559334[P].1983-10-20.
[6]Kazuo S,Jiro G.Process for the preparation of 7-[2-(2-aminothiazol-4-yl)-2-hydroxyimino-acetamido]-3-cephem compounds:CA,1340604[P].1999-06-22.
[7]Leeg S,Chang YK,Chun JP,et al.Process for preparation of Cefdinir:WO,97/24358[P].1991-10-07.
[8]蒋煜,张哲峰,王虹.β-内酰胺类抗生素异构体杂质研究和质控进展[J].中国抗生素杂志,2010,35(8):561-566.
[9]胡昌勤,蒋煜,张靖溥,等.对β-内酰胺抗生素中微量不稳定杂质研究策略与方法的思考[J].中国新药杂志,2013,22(1):4-12.
[10]中国药典2015年版.二部[S].2015:244-249.
[11]Llinás A,Vilanova B,Frau J,et al.Chemical reactivity of penicillins and cephalosporins.intramolecular involvement of the acyl-amido side chain[J].J Org Chem,1998,63(24):9052-9060.
[12]Okamoto Y,Kiriyama K,Namiki Y,et al.Degradation kinetics and isomerization of cefdinir,a new oral cephalosporin,in aqueous solution.1[J].J Pharm Sci,1996,85(9):976-983.
[13]Okamoto Y,Kiriyama K,Namiki Y,et al.Degradation kinetics and isomerization of cefdinir,a new oral cephalosporin,in aqueous solution.2.Hydrolytic degradation pathway and mechanism forβ-lactam ring opened lactones[J].JPharm Sci,1996,85(9):984-989.
[14]Indelicato JM,Norvilas TT,Pfeiffer RR,et al.Substituent effects upon the base hydrolysis of penicillins and cephalosporins.Competitive intramolecular nucleophilic amino attack in cephalosporins[J].J Med Chem,1974,17(5):523-527.