Separation and Determination of Methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection  

作　　者：WANGAn-bao JosephF.Foss YUANChun-su JoachimOsinski 

机构地区：[1]DepartmentofAnesthesiaandCriticalCare,TheUniversityofChicago,Chicago,IL60637,USA [2]DepartmentofAnesthesiaandCriticalCare,TheUniversityofChicago,Chicago,IL60637,USA／／ShanghaiInstituteofCeramics,ChineseAcademyofSciences,Shanghai200050,P.R.China

出　　处：《Chemical Research in Chinese Universities》2005年第3期268-273,共6页高等学校化学研究（英文版）

基　　金：SupportedbytheInstitutionalAmericanCancerSociety,theInternationalAnesthesiaResearchSocietyandClinicalPracticeEnhancementandAnesthesiaResearchFoundation.

摘　　要：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 c_~max =206.42(±16.53) ng/mL and t_~max =60 min.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 c_~max =206.42(±16.53) ng/mL and t_~max =60 min.

关 键 词：Liquid chromatography Electrochemical detection METHYLNALTREXONE PHARMACEUTICAL SERUM Biological analysis 

分 类 号：R974[医药卫生—药品] Q592.1[医药卫生—药学]