液相層析／質譜儀在測量人體血漿中Procaterol藥物濃度之探討   全文下載

A Novel Liquid Chromatography/Mass/Mass Spectrometry System to Determine Procaterol Levels in Human Plasma

本研究旨在開發一具有高靈敏度和準確度之液相層析/質譜儀方法，作為測量procaterol在人體內之藥物血中濃度。本分析方法之層析條件包括c18的層析管柱，移動相為10 mM醋酸胺/乙?（30/70, v/v），流速1.0 mL/min。Procaterol和內部標準品betaxolol之質譜儀分析條件為：以游離子態模式（ionization mode; ESI+）進行、離子源溫度90°c、去溶劑（desolvation）溫度為500°c。雙質譜偵測器對procaterol的偵測為篩檢290.99（parent ion）和測量273.64（daughter ion），對betaxolol的偵測為篩檢308.33（parent ion）和測量116.31（daughter ion）。本法對血漿中之procaterol最低可偵測濃度和可定量濃度分別為0.001 ng/mL和0.005 ng/mL。以procaterol加入空白血漿配置成濃度範圍0.005~1.0 ng/mL之溶液，所建立的檢量線具有良好的線性關係，相關係數（r2）為0.9998。同日內（within-run）和異日間（between-run）精確度試驗結果指出，各組血漿溶液所測得濃度之變異係數（cV）均小於10.2%。Procaterol在各組人類血漿溶液的回收率均未低於86%。相對於已發表之動物體內procaterol分析之文獻，由本研究結果顯示，所提出之液相層析/質譜儀分析系統，是一具高靈敏度、高選擇性、高準確度的分析方法，可用於探討procaterol於人體內之藥物動力學特性。"

A highly sensitive and accurate liquid chromatography/mass/mass spectrometry (LC/MS/MS) system was developed to determine the plasma concentration of procaterol in human subjects. The chromatographic system used for this study included a Lichrospher® Silica column with a mobile phase of 10 mM ammonium acetate aqueous solution/acetonitrile (30/70, v/v) and 1.0 mL/min flow-rate. Procaterol and betaxolol, the latter used as the internal standard, were detected using mass spectrometry at ionization mode (ESI+), a source block temperature of 90°C and desolvation temperature of 500°C. The detection mass was 290.99 > 273.64 for procaterol and 308.33 > 116.31 for betaxolol. The calibration curve over a concentration range of 0.005~1.0 ng/mL showed good linearity, with a correlation coefficient of 0.9998. The results of within-run and between-run precision tests for the method have coefficient variation values of no more than 10.2%. The average recovery rates of procaterol in human plasma samples over a wide range of concentrations exceeded 86%. The concentration detection and quantitation limits of the proposed LC/MS/MS method were determined to be 0.001 and 0.005 ng/mL, respectively. The pharmacokinetic parameters from volunteers were similar to that previously reported in the literature in a study on patients administered with the same procaterol HCl dose. All results indicate that the LC/MS/MS method proposed in this study is a sensitive, selective, precise, and accurate method to determine concentrations of procaterol in human plasma and hence to evaluate the pharmacokinetic characteristics of human subjects.