HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY FOR THE SIMULTANEOUS ESTIMATION OF CEFOPERAZONE AND SULBACTAM IN RAT PLASMA AND ITS IMPORTANCE IN THERAPEUTIC DRUG MONITORING
Objective: To study the Therapeutic drug monitoring and pharmacokinetics of marketed antibiotics formulation by developing a sensitive and specific Bioanalytical Chromatographic method.
Methods: In the present study, we developed a rapid, sensitive and selective chromatographic method for simultaneous estimation of Cefoperazone (CEF) And Sulbactam (SAL) in male Wistar rat plasma. A novel liquid phase extraction method has adopted the preparation of plasma sample preparation. The CEF and SAL were eluted on a peerless Basic C18 (25 cm; 4.6 mm x 5 µm) column maintained at controlled environmental conditions. The gradient mobile phase comprised of 10 mmol ammonium acetate and acetonitrile. A UV detector was set at 250 nm and retention times for CEF and SAL were approximately 5.6 and 14.2 min, respectively. The proposed HPLC method was validated according to the US FDA guidelines with respect to the linearity, accuracy, precision, detection and quantitation limits, robustness and specificity.
Results: Calibration curves of CEF and SAL were linear across the concentration range of 600-1000 and 6-10 µg/ml, with correlation coefficients (r2)>0.9977 and (r2)>0.9987, respectively. The limits of detection for CEF and SAL were 70.48 and 0.35 µg/ml, respectively. Additionally, CEF and SAL were stable in plasma for at least 24 h when stored at room temperature and 2-8 °C.
Conclusion: The developed chromatographic method was effectively utilized to measure the plasma CEF and SAL concentrations in a pharmacokinetics study after intravenous injection to the healthy male Wistar rats.
2. Bardin C, Veal G, Paci A, Chatelut E, Astier A, Leveque D, et al. Therapeutic drug monitoring in cancer–are we missing a trick? Eur J Cancer 2014;50:2005-9.
3. MN Martinez, MG Papich, GL Drusano. Dosing regimen matters: the importance of early intervention rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemother 2012;56:2795-805.
4. JJ De Waele, S Carrette, M Carlier, V Stove, J Boelens, G Claeys I, et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial. Intensive Care Med 2014;40:380-7.
5. JA Roberts, SK Paul, M Akova, M Bassetti, Jan J, De Waele G, et al. DALI: defining antibiotic levels in intensive care unit patients: are current ?-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 2014;58:1072-83.
6. Wilbaux M, Fuchs A, Samardzic J, Rodieux F, Csajka C, Allegaert K, et al. Pharmacometric approaches to personalize use of primarily renally eliminated antibiotics in preterm and term neonates. Clin Pharm 2016;56:909-35.
7. Xiu Jun Wu, Xin Huang, Hai-Yan Shi, Xing-Kai Chen, Qian Dong, Guo-Xiang Hao, et al. Determination of cefoperazone and sulbactam in serum by HPLC-MS/MS: an adapted method for therapeutic drug monitoring in children. Biomedl Biography 2017;32:1-12.
8. Sreenivasulu E, G Tulja Rani. Validated RP-HPLC method for simultaneous estimation of sulbactam and cefoperazone in bulk and pharmaceutical dosage form. Int J Curr Res Chem Pharma Sci 2014;1:60–7.
9. B Dhandapani, N Thirumoorthy, Shaik Harun Rasheed, M Rama Kotaiah, KB Chandrasekhar. RP-HPLC method development and validation for the simultaneous estimation of cefoperazone and sulbactam in parenteral preparation. Int J Chem Tech Res 2010;2:752-5.
10. Sharma Amit Kumar, Dharamasi Abhay. Simultaneous high performance liquid chromatographic determination of sulbactam and cefoperazone in pharmaceutical dosage form. J Pharm Sci Innovation 2012;1:93-5.
11. Eglal A Abdelaleem, Ibrahim A Naguib, Hala E Zaazaa, Essraa A Hussein. Development and validation of HPLC and HPTLC methods for determination of cefoperazone and its related impurities. J Chromato Sci 2016;54:179–86.
12. Sanjay S Malgundkar, Saira Mulla. Validated HPTLC method for simultaneous determination of cefoperazone sodium and sulbactam sodium in combined dosage form. IOSR J Pharm Bio Sci 2014;9:60-5.
13. Yingjie Zhou, Jing Zhang, Beining Guo, Jicheng Yu, Yaoguo Shi, Minggui Wang, et al. Liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of cefoperazone and sulbactam in plasma and its application to a pharmacokinetic study. J Chromatogr B: Anal Technol Biomed Life Sci 2010;878:3119-24.
14. M Senthilraja, PN Sanjaypai. Spectrophotometric method for the determination of cefoperazone sodium in pharmaceutical formulations. Ind J Pharm Sci 2006;68:384-5.
15. Mervat M, Hosny. Development of simple green spectrophotometric method for determination of cefoperazone sodium and cefepime hydrochloride in bulk, pharmaceutical dosage forms and human urine. Asian J Pharm Clin Res 2014;7:145-50.
16. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.html Or http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm [Last accessed on 02 May 2020].
17. John J, Veillette S, Alexander Winans Steven C, Forland Victoria K, Maskiewicz. A simple and rapid RP-HPLC method for the simultaneous determination of piperacillin and tazobactam in human plasma. J Pharm Biomed Anal 2016;131:80-6.
18. Roberts JA, Ulldemolins M, Roberts MS, McWhinney B, Ungerer J, Paterson DL, et al. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. J Antimicrobial Agents 2010;36:332-9.
19. Brad Moriyama, Sameer Kadri, Stacey A Henning, Robert L Danner, Thomas J Walsh, Scott R Penzak. Therapeutic drug monitoring and genotypic screening in the clinical use of voriconazole. Curr Fungal Infect Rep 2015;9:74–87.
20. Germovsek E, Kent A, Metsvaht T, Lutsar I, Klein N, Turner MA, et al. Development and evaluation of a gentamicin pharmacokinetic model that facilitates opportunistic gentamicin therapeutic drug monitoring in neonates and infants. Antimicrob Agents Chemother 2016;60:4869-77.
21. Dong Y, Li Y, Zhang Y, Zhang T, Zhu L, Dong Y, et al. Cefoperazone/sulbactam therapeutic drug monitoring in patients with liver cirrhosis: potential factors affecting the pharmacokinetic/pharmacodynamic target attainment. Basic Clin Pharmacol Toxicol 2019;125:353-9.
22. Zhou Y, Zhang J, Guo B, Yu J, Shi Y, Wang M, et al. Liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of cefoperazone and sulbactam in plasma and its application to a pharmacokinetic study. J Chromatogr B: Anal Technol Biomed Life Sci 2010;878:3119-24.
23. Bawdon RE, Madsen PO. High-pressure liquid chromatographic assay of sulbactam in plasma, urine, and tissue. Antimicrob Agents Chemother 1986;30:231-3.
24. Zheng J, Liang L, Wang Z, Peng B, Li S, Lai J. Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential. Zhonghua Wai Ke Za Zhi 2014;52:775-80.
This work is licensed under a Creative Commons Attribution 4.0 International License.