亚胺培南浓度测定.docx

1、亚胺培南浓度测定1、色谱条件色谱柱:Nova PakC18反相(4 m, 1503.9 mm)流动相：12.4g 硼酸溶于1000ml水中加入1M Na OH pH 7.2.流速:1ml/min进样量:10 l.稳定剂:3-吗啉基丙磺酸（MOPS）：乙二醇：水（1：1：2） -40 15天内标：不需内标药代动力学参数：泰能参考文献：L. Garcia-Capdevila, C. Lopez-Calull, C. Arroyo,et.al. Determination of imipenem in plasma by high-performance liquid chromatography

2、for pharmacokinetic studies in patients Journal of Chromatography B, 692 (1997) 127132Fig. 1. (a) 空白人血浆色谱图 (b)标准人血浆与50 g/ml亚胺培南混合(peak1 =imipenem) 色谱图. (c) 滴注结束患者血浆色谱图(peak1=imipenem)标准曲线：0.1 到 100g/ ml. The limits of detection and quantitation were 0.03 and 0.08 mg/ ml.2、色谱条件（动物试验）色谱柱:Waters Atlant

3、is HILIC silica column (50mm2.1mm, 3 )流动相：80%乙腈加入15M甲酸铵(pH 3)流速:0.4 mL/min柱温:室温 进样量:10 l.内标：（只有分子结构式）稳定剂：1M 2-(N-吗啉代）-乙磺酸 (MES) pH6.0 与50%乙二醇1：1(v/v) 混合，1M MES是将10.88g MES酸（分子量（MW）：195.2）和9.62g MES钠盐（MW: 217.2）溶于100ml Milli-Q水而成-70储存亚胺培南最有效的是兼性离子溶液如血浆样品用2-（N吗啉代）乙磺酸，(MES) pH 6.0； 3-吗啉基丙磺酸（MOPS）pH 7.2

4、；或者4-(2-hydroxyethyl) piperazineethanesulfonic acid (HEPES) pH 7.0质谱条件离子检测方式:离子极性:阳离子(positive)离子化方式:气动辅助电喷雾离子化（ESI）检测对象（亚胺培南、内标）:传输区电压:4.5kv干燥气流速:60 L/min雾化室压力:干燥气温度:550亚胺培南在生物基质（经酶催化）和水溶液中易水解，尤其实在酸性或碱性环境下。蛋白质沉淀可以最小化稳定性问题。参考文献：Yang Xu, Wei Xie, Cynthia M. Miller-Stein et.al.Hydrophilic interaction

5、chromatography/tandem mass spectrometry for the simultaneous determination of three polar non-structurally related compounds, imipenem, cilastatin and an investigational b-lactamase inhibitor,MK-4698, in biological matrices. Rapid Commun. Mass Spectrom,2009, 23: 21952203.琼脂法稳定剂：血样：2-（N吗啉代）乙磺酸，（MES）p

6、H6.0；尿样：3-（N吗啉代）丙磺酸（MOPS），PH6.81000mg)标准曲线： log y = 0.079 1.23参考文献：Andrea Novelli,1 Chiara Adembri,2 Paola Livi et.al.Pharmacokinetic Evaluation of Meropenem and Imipenem in Critically Ill Patients with Sepsis . Clin Pharmacokinet 2005; 44 (5): 539-5494.色谱条件（药品鉴定）色谱柱：采用Hypersil ODS 250mm 4.6mm(5m)流动

7、相：A相(0.01 mol/L磷酸二氢钾溶液)(用10氢氧化钾调节pH至73)，流动相B为甲醇，流速:每分钟1.5ml柱温:室温进样量:20l水：miliQ超纯水标准曲线:：亚胺培南自身对照溶液在供试品溶液0.2-1.2浓度范围内呈线性,线性范围为2-12g/L参考文献：赵玉新，王广慧，列丹等.HPLC法测定亚胺培南的有关物质.中国当代医药,2010,17(13):50-515、色谱条件色谱柱:Diamond C18(46ram250mm，5m)；分析纯：磷酸铵、磷酸二氢钾、盐酸、30过氧化氢、氢氧化钠色谱纯：乙腈流动相：乙腈0.1molL磷酸铵(精密称取磷酸钠2031mg，加1000ml水使

8、溶解并稀释至刻度，用磷酸调至pH68)(30：70)；流速:8mlmin柱温:50进样量:20l参考文献：王艳军.高效液相色谱法测定亚胺培南一西司他丁钠的含量中国美容医,2010,19(2):2546、色谱条件色谱柱:C18 10m, 3.9 x 300 mm流动相：2% 乙腈和98%磷酸盐 三乙胺缓冲液（ 含0.2%叠氮化钠）流速:1.0mlmin进样量:20l稳定剂：0.2ml 2-(N吗啉代)乙磺酸和等量乙二 醇,聚四氟乙烯封闭，-70药代动力学参数：500 mg every 6 hours标准曲线:The standard curve for plasma was linear bet

9、ween 0.3-50g/ml. 参考文献：David S.McKindley,Pharm.D.,BradleyA. et.al.Boucher,Pharmacokinetics of Aztreonam and Imipenem in Critically Ill Patients with Pneumonia.Pharmacotherapy ,1996,16(5):924-9317、色谱条件色谱柱:Bondasphere C 18 5 m (3.9 150 mm);流动相：10 m M磷酸缓冲液 (pH 6.5) 和乙腈 (197: 3, vol/vol)流速:1 ml/min柱温：40

10、C进样量:20l稳定剂：1 M 3-吗啉基丙磺酸 buffer (pH 7.0)标准曲线:The calibration curve was linear from 0.05 to 100 g/ml, and the lower limit of quantification was 0.05 g/ml.参考文献：Kazuro Ikawa ,Norifumi Morikawa, Kenichi Sakamoto et.al. Pharmacokinetics and Pharmacodynamic Assessment of Imipenem in the Intraperitoneal Fl

11、uid of Abdominal Surgery Patients .Chemotherapy, 2008,54:131139 8、色谱条件（动物试验）色谱柱:反相 4 m, 39 X 150 mm流动相：0.2M硼酸盐缓冲剂(pH, 7.2)流速:1.5 mL/min稳定剂：0.5M 3-吗啉基丙磺酸:水：乙二醇=2：1：1 -80，90天参考文献：Corrie W. Barker, Weijiang Zhang, Susan Sanchez, et.al.Pharmacokinetics of imipenem in dogs AJVR, 2003,6(64):694-6999、色谱条件（

12、体外试验）色谱柱:CAPCELL PAK C18 type MG 5 m (4.6 mm i.d.150 mm)流动相：0.04M 3-（N吗啉代）丙磺酸钠(MOPS Na)：1.0g己磺酸钠（每公升加上0.005gdisodium dihydrogen ethylendiamine tetraacetate dihydrate）加入0.1M NaOH调整pH至7.0流速:2.2 mL/min柱温：50C进样量:10 L参考文献：Miyako Yoshida, Yuko Takasu, Kaori Shimizu,et.al.Prediction of the Stability of Imi

13、penem in Intravenous Mixtures.Chem. Pharm. Bull.,2013,61(1): 1710、色谱条件色谱柱:SupelcosilTM LC-18：25 cm4.6mm5 m,流动相：0.075M 醋酸:乙腈(92:8, v/v), pH 5.0 .流速:0.8 ml/min柱温：37进样量:5 L稳定剂： 3-N-吗啉代丙磺酸 (MOPS) 80 C内标：头孢呋辛标准曲线:1 g every 6 h.烧伤患者the intercept 0.0196 (SEM: 0.0007) and slope 0.0841 (SEM: 0.0029) for imip

14、enem (r2: 0.999), both over 0.4100 g/ml concentration range.The LOQ was 0.4 g/ml for vancomycin and imipenem.The LOD was 0.2 g/ml for vancomycin and imipenem.参考文献：K.J. Vera Lopez , D. Faria Bertoluci , K.M. Vicente,et.al.Simultaneous determination of cefepime, vancomycin and imipenem in human plasma

15、 of burn patients by high-performance liquid chromatography. Journal of Chromatography B,2007, 860: 24124511、色谱条件(VAP患者)流动相：0.2M硼酸pH 7.2,流速:1 mL/min柱温：进样量:10 L稳定剂：0.5 M MOPS/water/ethylene glycol,2:1:1, v/v/v 80 CFigure 1. Mean plasma imipenem concentrationtime data for nine patients with VAP follow

16、ing administration of: 0.5 g, 0.5 h infusion (三角形);0.5 g, 2 h infusion (菱形); and 1 g, 2 h infusion (方形).参考文献:Sutep Jaruratanasirikul and Teeratad Sudsai.Comparison of the pharmacodynamics of imipenem in patients with ventilator-associated pneumonia following administration by 2 or 0.5 h infusion. Jo

17、urnal of Antimicrobial Chemotherapy 2009, 63: 5605637、色谱条件色谱柱:Grom-SIL 80 Amino-3 CP, 5m, 40 4.6 mm;流动相：0.01 M醋酸铵和乙腈(1:1 vol:vol)流速:柱温：进样量:稳定剂：1M吗啉基丙磺酸(pH 7.0) _70C.内标：标准曲线:The response from calibration standards was linear from 0.100 to100.0 mg/liter, and the coefficient of correlation for all measured sequences was at least 0.997.质谱条件离子检测方式:离子极性:阳离子(positive)离子化方式:气动辅助电喷雾离子化（ESI）检测对象（亚胺培南、内标）:imipenem, m/z：300m/z 98,internal standard, m/z 3513m/z 265传输区电压:干燥气流速:雾化室压力:干燥气温度: