高效液相色谱-质谱联用法(HPLC-MS/MS)测定CRRT时血浆哌拉西林/他唑巴坦浓度
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摘要
目的建立准确、灵敏的高效液相色谱-质谱联用法(high performance liquid chromatography-mass spectrometry,HPLC-MS/MS)测定持续肾脏替代(continuous renal replacement, CRRT)时人血浆中哌拉西林钠/他唑巴坦钠的浓度。方法选用高、低两种剂量给药,采取单制剂双周期序贯试验设计,对12例行CRRT患者完成哌拉西林/他唑巴坦钠静脉滴注之后,使用HPLC-MS/MS方法同时测定哌拉西林及他唑巴坦的浓度。采用Gemini C18(50mm×3.0 mm,3μm)分析柱;流动相为甲醇:乙腈:水:1 mol/L氨水:甲酸(25∶15∶60∶0.1∶0.05),质谱检测采用电喷雾离子源,多反应离子监测(MRM)模式检测。结果血浆中哌拉西林线性范围为1～100 mg/L,他唑巴坦线性范围为0.5～40.0 mg/L,高、中、低3个浓度日内及日间精密度均小于5%。实测12例行CRRT患者,血药浓度与给药剂量呈相关性。结论高效液相色谱-质谱联用法灵敏度高、特异性好,可以运用于脓毒症患者接受CRRT时血浆哌拉西林/他唑巴坦浓度的测定。
Objective To establish an accurate and sensitive high performance liquid chromatography-mass spectrometry(HPLC-MS/MS) for the determination of piperacillin in human plasma the concentration of sodium/tazobactam sodium during continuous renal replacement(CRRT). Methods The high-dose and low-dose two-dose method were used to design a single-dose two-cycle sequential test. After 12 patients with CRRT were treated with piperacillin/tazobactam sodium intravenously, HPLC-MS/MS was used simultaneously to determine the concentrations of piperacillin and tazobactam. The Gemini C18(50 mm×3.0 mm, 3 μm) analytical column was used. The mobile phase was methanol, acetonitrile, water, 1 mol/L ammonia, formic acid(25∶15∶60∶0.1∶0.05). Mass spectrometry was detected using an electrospray ion source and multiple reactive ion monitoring(MRM) mode. Results The linear range of piperacillin in plasma was 1-100 mg/L, and the linear range of tazobactam was 0.5～40.0 mg/L. The intra-day and inter-day precision of high, medium and low concentrations were less than 5%. The blood concentration of 12 patients who underwent CRRT was correlated with the dose. Conclusion High performance liquid chromatography-mass spectrometry has high sensitivity and specificity, and can be used to determine the plasma concentration of piperacillin/tazobactam in patients with sepsis receiving CRRT.
Objective To establish an accurate and sensitive high performance liquid chromatography-mass spectrometry(HPLC-MS/MS) for the determination of piperacillin in human plasma the concentration of sodium/tazobactam sodium during continuous renal replacement(CRRT). Methods The high-dose and low-dose two-dose method were used to design a single-dose two-cycle sequential test. After 12 patients with CRRT were treated with piperacillin/tazobactam sodium intravenously, HPLC-MS/MS was used simultaneously to determine the concentrations of piperacillin and tazobactam. The Gemini C18(50 mm×3.0 mm, 3 μm) analytical column was used. The mobile phase was methanol, acetonitrile, water, 1 mol/L ammonia, formic acid(25∶15∶60∶0.1∶0.05). Mass spectrometry was detected using an electrospray ion source and multiple reactive ion monitoring(MRM) mode. Results The linear range of piperacillin in plasma was 1-100 mg/L, and the linear range of tazobactam was 0.5～40.0 mg/L. The intra-day and inter-day precision of high, medium and low concentrations were less than 5%. The blood concentration of 12 patients who underwent CRRT was correlated with the dose. Conclusion High performance liquid chromatography-mass spectrometry has high sensitivity and specificity, and can be used to determine the plasma concentration of piperacillin/tazobactam in patients with sepsis receiving CRRT.
引文
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[13]Stamm RA,Fazili Z,Pfeiffer CM.Addition of Exogenousγ-Glutamyl Hydrolase Eliminates the Need for Lengthy Incubation of Whole-Blood Lysate for Quantitation of Folate Vitamers by High-Performance Liquid Chromatography-Tandem Mass Spectrometry[J].Curr Dev Nutr,2017,2(1):1-9.
[14]Hao JY,Wan Y,Yao XH,et al.Effect of different planting areas on the chemical compositions and hypoglycemic and antioxidant activities of mulberry leaf extracts in Southern China[J].PLoS One.2018,13(6):e0198072.
[15]Novotna B,Abdel-Hamid M,Koblizek V,et al.A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD[J].Adv Clin Exp Med,2018,27(4):531-539.
[16]Wang Z,Olenyuk BZ,Shih JC,et al.Quantifica tion and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry[J].J Pharm Anal,2018,8(3):153-159.
[17]Sobeh M,Mahmoud MF,Hasan RA,et al.Tannin-rich extracts from Lannea stuhlmannii and Lannea humilis(Anacardiaceae)exhibit hepatoprotective activities in vivo via enhancement of the anti-apoptotic protein Bcl-2[J].Sci Rep,2018,8(1):9343.
[18]Chirollo C,Vassallo A,Dal Piaz F,et al.Investigation of the Persistence of Penicillin G and Dihydrostreptomycin Residues in Milk of Lactating Buffaloes(Bubalus bubalis)Using Ultra-High-Performance Liquid Chromatography and Tandem Mass Spectrometry[J].J Agric Food Chem,2018,66(25):6388-6393.
[19]Boonya-Atichart A,Boontanon SK,Boontanon N.Study of hybrid membrane filtration and photocatalysis for removal of perfluorooctanoic acid(PFOA)in groundwater[J].Water Sci Technol,2018,2017(2):561-569.
[20]Hongkachok C,Boontanon SK,Boontanon N,et al.Levels of perfluorinated compounds(PFCs)in groundwater around improper municipal and industrial waste disposal sites in Thailand and health risk assessment[J].Water Sci Technol,2018,2017(2):457-466.
[2]Valtonen M,Tiula E,Takkunen O,et al.Elimination of the Piperacillin/Tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure[J].J Antimicrob Chemother,2001,48(6):881-885.
[3]陈怀生,王薇,温隽珉,等.亚胺培南/西司他丁与哌拉西林/他唑巴坦治疗30例脓毒症患者疗效比较[J].临床合理用药杂志,2011,4(36):17-19.
[4]许伟石,邓诗琳,韩春茂,等.哌拉西林/他唑巴坦防治烧伤感染的多中心临床试验[J].中华烧伤杂志,2002,18(2):75-77.
[5]向松涛,王树声,甘澍,等.经皮肾镜取石术后尿脓毒症休克的诊治特点分析[J].中华泌尿外科杂志,2010,31(8):520-523.
[6]任敏蒲,刘岚,李丽,等.儿童肺炎克雷伯菌脓毒症临床特点及细菌耐药性分析[J].中国抗生素杂志,2013,38(4):280-284.
[7]卢中秋,邱巧檬.创伤弧菌脓毒症治疗的研究现状[J].世界急危重病医学杂志,2004,20(3):226-229.
[8]陈科.哌拉西林钠他唑巴坦用于重症脓毒症感染治疗效果探讨[J].中国医学工程,2014,16(8):88-89.
[9]T Nakada,S Oda,K Matsuda,et al.Continuous hemodiafiltration with PMMA hemofilter in treatment of patients with septic shock[J].Mol Med,2008,14(5-6):257-263.
[10]Vincent JL.Adjustment of antimicrobial regimen in critically ill patients undergoing continuous renal replacement therapy[M].Yearbook of Intensive Care And Emergency Medicine.Berlin:Springer,2007:592-608.
[11]范珠.哌拉西林他唑巴坦人体药动学研究[J].中国药业,2016,25(9):5-8.
[12]Lind PM,Salihovic S,Stubleski J,et al.Changes in plasma levels of perfluoroalkyl substances(PFASs)are related to increase in carotid intima-media thickness over 10years-a longitudinal study[J].Environ Health,2018,17(1):59.
[13]Stamm RA,Fazili Z,Pfeiffer CM.Addition of Exogenousγ-Glutamyl Hydrolase Eliminates the Need for Lengthy Incubation of Whole-Blood Lysate for Quantitation of Folate Vitamers by High-Performance Liquid Chromatography-Tandem Mass Spectrometry[J].Curr Dev Nutr,2017,2(1):1-9.
[14]Hao JY,Wan Y,Yao XH,et al.Effect of different planting areas on the chemical compositions and hypoglycemic and antioxidant activities of mulberry leaf extracts in Southern China[J].PLoS One.2018,13(6):e0198072.
[15]Novotna B,Abdel-Hamid M,Koblizek V,et al.A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD[J].Adv Clin Exp Med,2018,27(4):531-539.
[16]Wang Z,Olenyuk BZ,Shih JC,et al.Quantifica tion and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry[J].J Pharm Anal,2018,8(3):153-159.
[17]Sobeh M,Mahmoud MF,Hasan RA,et al.Tannin-rich extracts from Lannea stuhlmannii and Lannea humilis(Anacardiaceae)exhibit hepatoprotective activities in vivo via enhancement of the anti-apoptotic protein Bcl-2[J].Sci Rep,2018,8(1):9343.
[18]Chirollo C,Vassallo A,Dal Piaz F,et al.Investigation of the Persistence of Penicillin G and Dihydrostreptomycin Residues in Milk of Lactating Buffaloes(Bubalus bubalis)Using Ultra-High-Performance Liquid Chromatography and Tandem Mass Spectrometry[J].J Agric Food Chem,2018,66(25):6388-6393.
[19]Boonya-Atichart A,Boontanon SK,Boontanon N.Study of hybrid membrane filtration and photocatalysis for removal of perfluorooctanoic acid(PFOA)in groundwater[J].Water Sci Technol,2018,2017(2):561-569.
[20]Hongkachok C,Boontanon SK,Boontanon N,et al.Levels of perfluorinated compounds(PFCs)in groundwater around improper municipal and industrial waste disposal sites in Thailand and health risk assessment[J].Water Sci Technol,2018,2017(2):457-466.