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Separation and Determination of Methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection
作者姓名:WANG An-bao~  *  Joseph F. Foss  YUAN Chun-su and Joachim Osinski .
作者单位:WANG An-bao~1,2*,Joseph F. Foss1,YUAN Chun-su1 and Joachim Osinski1 1. Department of Anesthesia and Critical Care,The University of Chicago,Chicago,IL 60637,USA; 2. Shanghai Institute of Ceramics,Chinese Academy of Sciences,Shanghai 200050,P. R. China
基金项目:SupportedbytheInstitutionalAmericanCancerSociety,theInternationalAnesthesiaResearchSocietyandClinicalPracticeEnhancementandAnesthesiaResearchFoundation.
摘    要:Introduction Opioidmedicationsarewidelyusedclinically forrelievingpainandasantidiarrhealsandantitus- sives.Opioidantagonistsconsistofagroupofnat- ural,semisynthetic,orsyntheticcompoundsacting onaseriesofreceptors.Concomitantwiththeabil- itytorelievepain,thesedrugshaveadverseef- fects.Side-effectsofopioidtreatmentincludenau- sea,constipation,urinaryretention,pruritus,fa- tigue,psychomimeticdisturbance,difficultmic- turition,vomitinganddependence.Thesesideef- fectsareoftensevereenoughtolimitthe…

关 键 词:甲基环丙甲羟二羟吗啡酮  人体  血浆  高性能液体色谱  电化学探测技术  药物  止咳药
收稿时间:2004-09-06

Separation and Determination of Methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection
WANG An-bao,*,Joseph F. Foss,YUAN Chun-su and Joachim Osinski ..Separation and Determination of Methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection[J].Chemical Research in Chinese University,2005,21(3):268-273.
Authors:WANG An-bao  Joseph F Foss  YUAN Chun-Su  Joachim Osinski
Institution:1. Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA;
2. Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China
Abstract:A high performance liquid chromatography(HPLC) method coupled with electrochemical detection and solid phase extraction is described for the separation and determination of methylnaltrexone(MNTX), a quaternary opioid antagonist, in human clinical plasma samples after oral administration. Linearity of the standard curve for MNTX was found in the range of 4.0_150 ng/mL and was statistically conformed. The correlation coefficient(r2) and calibration equation obtained from linear regression analysis are 0.9999 and Y=54.27X-0.22, where Y and X represent the peak area and concentration of MNTX, respectively. The detection limit of MNTX under the present experimental conditions is 2.0 ng/mL by estimating at a ratio of 3 of signal to noise. The mean recovery of MNTX in human plasma is higher than 97%. The analytical method was applied to the pharmacokinetic determination of MNTX after single dose oral administration. These data demonstrate that the change of MNTX plasma concentration versus time is obvious. MNTX level of plasma reaches to a plateau between 45 to 120 minutes and then falls slowly. The content of MNTX in plasma sample maintains at an obviously detectable level after twelve hours of oral administration. The pharmacokinetic parameters for a single dose of 19.2 mg/kg in plasma are cmax=206.42(±16.53) ng/mL and tmax=60 min.
Keywords:Liquid chromatography  Electrochemical detection  Methylnaltrexone  Pharmaceutical  Serum  Biological analysis
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