HPLC-DAD法同时测定注射用头孢他啶阿维巴坦钠复方制剂的含量
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摘要
目的:首次建立一种HPLC-DAD法用于测定新型抗菌药物复方制剂———注射用头孢他啶阿维巴坦钠中2个组分的含量。方法:采用Kromasil C_(18)(250 mm×4.6 mm,5μm)为色谱柱;流动相A为30mmol·L~(-1)磷酸氢二钠-20 mmol·L~(-1)磷酸二氢钾缓冲液,流动相B为30 mmol·L~(-1)磷酸氢二钠和20 mmol·L~(-1)磷酸二氢钾的缓冲液-乙腈(50∶50),流动相A-流动相B(85∶15);流速为1.0 m L·min~(-1);柱温为40℃;检测波长为200 nm;进样量为10μL。结果:头孢他啶和阿维巴坦分别在0.005～1.0 mg·m L~(-1)(r=0.999 9)和0.006～1.0 mg·m L~(-1)(r=0.999 9)的浓度范围内线性关系良好。头孢他啶和阿维巴坦的平均加样回收率分别为99.2%(RSD=1.2%,n=3)和98.7%(RSD=3.1%,n=3),检测限分别为2μg·m L~(-1)和1μg·m L~(-1),两者的日内和日间精密度均小于1.5%。注射用头孢他啶阿维巴坦钠是由头孢他啶、阿维巴坦和碳酸钠组成的混合物,由于特殊灌装工艺及物理性质上的差异会造成三者在样品瓶中分布不均匀,建议采用整瓶稀释法测定该抗菌药物复方制剂的含量。结论:本研究建立的注射用头孢他啶阿维巴坦钠含量测定方法快速准确且重现性好,可用于常规质控实验室的日常检定。
Objective:To develop an HPLC coupled with diode array detection(DAD)method for the simultaneous determination of new antibiotic combination ceftazidime and avibactam for injection.Methods:The column was Kromasil C_(18)(250 mm×4.6 mm,5μm).The mobile phase A was phosphate buffer containing 30mmol·L~(-1)disodium hydrogen phosphate and 20 mmol·L~(-1)potassium dihydrogen phosphate,the mobile phase B was phosphate buffer(30 mmol·L~(-1)disodium hydrogen phosphate and 20 mmol·L~(-1)potassium dihydrogen phosphate)and acetonitrile(50∶50).The ratio of mobile phases A and B was 85∶15 at a flow rate of 1.0 m L·min~(-1).The column temperature was 40℃.The detection wavelength was 200 nm.The injection volume was10μL.Results:Ceftazidime and avibactam have good linear relation in the concentration range of 0.005～1.0mg·m L~(-1)(r=0.999 9)and 0.006～1.0 mg·m L~(-1)(r=0.999 9),respectively.The recovery rates of ceftazidime and avibactam were 99.2%(RSD=1.2%,n=3)and 98.7%(RSD=3.1%,n=3),respectively.The limits of detection(LODs)of ceftazidime and avibactam were 2μg·m L~(-1)and 1μg·m L~(-1),respectively.The RSD of intra-and inter-day was less than 1.5%.Ceftazidime and avibactam for injection is composed of ceftazidime,avibactam and sodium carbonate.The special filling process and different physical properties could cause misdistribution of the three components in the injection bottle.Therefore,a whole bottle dilution method was proposed for the determination of the antibiotic combination.Conclusion:The HPLC-DAD method of determination of ceftazidime and avibactam for injection developed in this study was fast,accurate and reproducible,which could be employed for daily identification in the routine quality control laboratory.
Objective:To develop an HPLC coupled with diode array detection(DAD)method for the simultaneous determination of new antibiotic combination ceftazidime and avibactam for injection.Methods:The column was Kromasil C_(18)(250 mm×4.6 mm,5μm).The mobile phase A was phosphate buffer containing 30mmol·L~(-1)disodium hydrogen phosphate and 20 mmol·L~(-1)potassium dihydrogen phosphate,the mobile phase B was phosphate buffer(30 mmol·L~(-1)disodium hydrogen phosphate and 20 mmol·L~(-1)potassium dihydrogen phosphate)and acetonitrile(50∶50).The ratio of mobile phases A and B was 85∶15 at a flow rate of 1.0 m L·min~(-1).The column temperature was 40℃.The detection wavelength was 200 nm.The injection volume was10μL.Results:Ceftazidime and avibactam have good linear relation in the concentration range of 0.005～1.0mg·m L~(-1)(r=0.999 9)and 0.006～1.0 mg·m L~(-1)(r=0.999 9),respectively.The recovery rates of ceftazidime and avibactam were 99.2%(RSD=1.2%,n=3)and 98.7%(RSD=3.1%,n=3),respectively.The limits of detection(LODs)of ceftazidime and avibactam were 2μg·m L~(-1)and 1μg·m L~(-1),respectively.The RSD of intra-and inter-day was less than 1.5%.Ceftazidime and avibactam for injection is composed of ceftazidime,avibactam and sodium carbonate.The special filling process and different physical properties could cause misdistribution of the three components in the injection bottle.Therefore,a whole bottle dilution method was proposed for the determination of the antibiotic combination.Conclusion:The HPLC-DAD method of determination of ceftazidime and avibactam for injection developed in this study was fast,accurate and reproducible,which could be employed for daily identification in the routine quality control laboratory.
引文
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[2] CDC. Antibiotic resistance threats in the United States[R]. Atlanta:2013.
[3] BUSH K. Game changers:newβ-lactamase inhibitor combinations targeting antibiotic resistance in gram-negative bacteria[J].ACS Infect Dis,2018,4(2):84-87.
[4]林惠贞,方松柏,赵宏伟,等.治疗革兰阴性细菌感染的新型抗菌药物头孢他啶-阿维巴坦[J].医药导报,2016,35(7):735-739.
[5] PRNewswire. FDA approves new antibacterial drug Avycaz[EB/OL].[2018-02-01]. https://www. drugs. com/newdrugs/fda-approves-avycaz-ceftazidime-avibactam-patients-hospital-acquired-bacterial-pneumonia-ventilator-4689. html
[6] HOLYK A,BELDEN V,LEE J,et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis:a case report[J]. J Antimicrob Chemother,2018,73(1):254-256.
[7] HIDALGO JA,VINLUAN CM,ANTONY N. Ceftazidime/avibactam:a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections[J]. Drug Des Devel Ther,2016,10(1):2379-2386.
[8] DESHPANDE D,SRIVASTAVA S,CHAPAGAIN M,et al.Ceftazidime-avibactam has potent sterilizing activity against highly drug-resistant tuberculosis[J]. Sci Adv, 2017, 3(8):e1701102.
[9] PHILIPPE LW,ANDREW W,KARLOWSKY JA. Ceftazidimeavibactam:an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections[J]. Core Evid,2014,9:13-25.
[10] GUGLIANDOLO A,CAIO C,MEZZATESTA ML. Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella pneumoniae infection in a patient with traumatic brain injury:A case report[J]. Med,2017,96(31):e7664.
[11] ROSSI F,CURY AP,MRG F,et al. The in vitro activity of ceftazidime-avibactam against 417 Gram-negative bacilli collected in 2014 and 2015 at a teaching hospital in S2o Paulo,Brazil[J].Braz J Infect Dis,2017,21(5):569-573.
[12]曾志旋,曹胜华,陈林.新型β-内酰胺酶抑制剂——阿维巴坦的研究进展[J].国外医药抗生素分册,2014,35(2):58-62.
[13] MACVANE SH,CRANDON JL,NICHOLS WW,et al. In vivo efficacy of humanized exposures of ceftazidime-avibactam in comparison with ceftazidime against contemporary enterobacteriaceae isolates[J]. Antimicrob Agents Chemother,2014,58(11):6913-6919.
[14] STACHYRA T,PECHEREAU MC,BRUNEAU JM,et al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104,a novel non-betalactam beta-lactamase inhibitor[J]. Antimicrob Agents Chemother,2010,54(12):5132-5138.
[15] BONNEFOY A,DUPUIS HC,STEIER V,et al. In vitro activity of AVE1330A,an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor[J]. J Antimicrob Chemother,2004,54(2):410-417.
[16]国家药典委员会.中华人民共和国药典[S]. 2015年版.第四部.北京:中国医药科技出版社,2015.
[17] The European Directorate for the Quality of Medicines and Healthcare(EDQM). European Pharmacopoeia 9th Edition[S]. 2016.N9rdlingen. German,2016:1996-2000.
[18] The United States pharmacopoeia convention. U. S. Pharmacopoeia[S]. 2016. Baltimore(USA),2016:3300-3303.
[19] HENRIK S,RICHARD M,REBECCA S,et al. Determination of avibactam and ceftazidime in human plasma samples by LC-MS[J]. Bioanalysis,2015,7(12):1423-1434.
[20] ICH. ICH harmonised tripartite guideline,Validation of analytical procedures:Text and Methodology Q2(R1),Complementary Guideline on Methodology[EB/OL].[1996-11-06]. http://www. ich. org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline. pdf.
[2] CDC. Antibiotic resistance threats in the United States[R]. Atlanta:2013.
[3] BUSH K. Game changers:newβ-lactamase inhibitor combinations targeting antibiotic resistance in gram-negative bacteria[J].ACS Infect Dis,2018,4(2):84-87.
[4]林惠贞,方松柏,赵宏伟,等.治疗革兰阴性细菌感染的新型抗菌药物头孢他啶-阿维巴坦[J].医药导报,2016,35(7):735-739.
[5] PRNewswire. FDA approves new antibacterial drug Avycaz[EB/OL].[2018-02-01]. https://www. drugs. com/newdrugs/fda-approves-avycaz-ceftazidime-avibactam-patients-hospital-acquired-bacterial-pneumonia-ventilator-4689. html
[6] HOLYK A,BELDEN V,LEE J,et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis:a case report[J]. J Antimicrob Chemother,2018,73(1):254-256.
[7] HIDALGO JA,VINLUAN CM,ANTONY N. Ceftazidime/avibactam:a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections[J]. Drug Des Devel Ther,2016,10(1):2379-2386.
[8] DESHPANDE D,SRIVASTAVA S,CHAPAGAIN M,et al.Ceftazidime-avibactam has potent sterilizing activity against highly drug-resistant tuberculosis[J]. Sci Adv, 2017, 3(8):e1701102.
[9] PHILIPPE LW,ANDREW W,KARLOWSKY JA. Ceftazidimeavibactam:an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections[J]. Core Evid,2014,9:13-25.
[10] GUGLIANDOLO A,CAIO C,MEZZATESTA ML. Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella pneumoniae infection in a patient with traumatic brain injury:A case report[J]. Med,2017,96(31):e7664.
[11] ROSSI F,CURY AP,MRG F,et al. The in vitro activity of ceftazidime-avibactam against 417 Gram-negative bacilli collected in 2014 and 2015 at a teaching hospital in S2o Paulo,Brazil[J].Braz J Infect Dis,2017,21(5):569-573.
[12]曾志旋,曹胜华,陈林.新型β-内酰胺酶抑制剂——阿维巴坦的研究进展[J].国外医药抗生素分册,2014,35(2):58-62.
[13] MACVANE SH,CRANDON JL,NICHOLS WW,et al. In vivo efficacy of humanized exposures of ceftazidime-avibactam in comparison with ceftazidime against contemporary enterobacteriaceae isolates[J]. Antimicrob Agents Chemother,2014,58(11):6913-6919.
[14] STACHYRA T,PECHEREAU MC,BRUNEAU JM,et al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104,a novel non-betalactam beta-lactamase inhibitor[J]. Antimicrob Agents Chemother,2010,54(12):5132-5138.
[15] BONNEFOY A,DUPUIS HC,STEIER V,et al. In vitro activity of AVE1330A,an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor[J]. J Antimicrob Chemother,2004,54(2):410-417.
[16]国家药典委员会.中华人民共和国药典[S]. 2015年版.第四部.北京:中国医药科技出版社,2015.
[17] The European Directorate for the Quality of Medicines and Healthcare(EDQM). European Pharmacopoeia 9th Edition[S]. 2016.N9rdlingen. German,2016:1996-2000.
[18] The United States pharmacopoeia convention. U. S. Pharmacopoeia[S]. 2016. Baltimore(USA),2016:3300-3303.
[19] HENRIK S,RICHARD M,REBECCA S,et al. Determination of avibactam and ceftazidime in human plasma samples by LC-MS[J]. Bioanalysis,2015,7(12):1423-1434.
[20] ICH. ICH harmonised tripartite guideline,Validation of analytical procedures:Text and Methodology Q2(R1),Complementary Guideline on Methodology[EB/OL].[1996-11-06]. http://www. ich. org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline. pdf.