PDF(Pubmed)
Abstract：
UNASSIGNED: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum.
UNASSIGNED: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument.
UNASSIGNED: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 μg/mL for MPA, 0.1-12 μg/mL for posaconazole, and 0.2-24 μg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 μg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems.
UNASSIGNED: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.
UNASSIGNED: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument.
UNASSIGNED: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 μg/mL for MPA, 0.1-12 μg/mL for posaconazole, and 0.2-24 μg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 μg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems.
UNASSIGNED: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.
摘要：
■作为常用免疫抑制剂的活性代谢物，通常监测霉酚酸(MPA)水平以防止移植后的器官排斥。三唑通常用于治疗免疫受损患者的侵袭性真菌感染。由于个体药代动力学和药物-药物相互作用的可变性，治疗药物监测建议三唑类抗真菌药。已经开发了可以定量血清中的MPA和三唑药物的多重LC-MS/MS测定。
■建立样品制备程序以加入内标化合物并沉淀蛋白质。反相色谱分离在C18柱上进行,每个样品的分析时间为5分钟。质谱仪以多反应监测模式操作。该方法在与TripleQuad6500或API4000仪器连接的两个HPLC系统上进行了验证。
■多重测定在宽动态范围内呈线性，MPA的分析物测量范围为0.4-48μg/mL，泊沙康唑0.1-12μg/mL，伏立康唑为0.2-24μg/mL，伊曲康唑,羟基伊曲康唑，和伊沙武康唑.日内和日内的不精确度不到10%。检测限低于0.04ug/mL,定量限低于0.2μg/mL。方法与当前内部方法的比较研究符合验收标准。仪器比较研究表明，从两个系统收集的数据之间存在很强的相关性。
■开发并验证了一种强大的多重LC-MS/MS测定法，用于在临床实验室中监测MPA和三唑药物水平。在两种不同仪器上的测定性能是可接受的和可比较的。
■建立样品制备程序以加入内标化合物并沉淀蛋白质。反相色谱分离在C18柱上进行,每个样品的分析时间为5分钟。质谱仪以多反应监测模式操作。该方法在与TripleQuad6500或API4000仪器连接的两个HPLC系统上进行了验证。
■多重测定在宽动态范围内呈线性，MPA的分析物测量范围为0.4-48μg/mL，泊沙康唑0.1-12μg/mL，伏立康唑为0.2-24μg/mL，伊曲康唑,羟基伊曲康唑，和伊沙武康唑.日内和日内的不精确度不到10%。检测限低于0.04ug/mL,定量限低于0.2μg/mL。方法与当前内部方法的比较研究符合验收标准。仪器比较研究表明，从两个系统收集的数据之间存在很强的相关性。
■开发并验证了一种强大的多重LC-MS/MS测定法，用于在临床实验室中监测MPA和三唑药物水平。在两种不同仪器上的测定性能是可接受的和可比较的。
