Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, 556 Morris Avenue, Summit, NJ 07901, USA.
J Pharm Biomed Anal. 2011 May 15;55(2):349-59. doi: 10.1016/j.jpba.2011.01.045. Epub 2011 Feb 24.
SCH 530348 is a safe and effective oral anti-platelet agent for patients with acute coronary syndrome. Clinical study results suggest that SCH 530348 dosage at 20 mg or 40 mg is feasible to achieve rapid maximum platelet inhibition following an acute coronary event or intervention procedure. To permit accurate determinations of circulating SCH 530348 in plasma following dosing, a method for measuring SCH 530348 concentrations in human plasma was validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method utilized semi-automated 96-well protein precipitation with gradient chromatography using an ACQUITY™ UPLC BEH C18 (2.1 mm×50 mm, 1.7 μm) column. The retention time of SCH 530348 was approximately 1.5 min. This method was validated for routine quantitation of SCH 530348 over the concentration range of 1.00-1000 ng/mL. Inter-run accuracy based on mean percent theoretical for replicate quality control samples was better than 95.2%. Inter-run precision based on percent relative deviation for replicate quality control samples was ≤3.3%. SCH 530348 quality control samples were stable in human plasma for up to three freeze/thaw cycles, for at least 467 days when frozen at -20 °C and for at least 7 h when stored at room temperature. The lower limit of quantitation was 1.00 ng/mL for a 100 μL plasma aliquot.
SCH 530348 是一种安全有效的急性冠脉综合征患者口服抗血小板药物。临床研究结果表明，SCH 530348 在 20mg 或 40mg 剂量下，在急性冠脉事件或介入手术后可快速达到最大血小板抑制。为了在给药后准确测定血浆中的循环 SCH 530348，采用液相色谱-串联质谱法（LC-MS/MS）验证了一种用于测量人血浆中 SCH 530348 浓度的方法。该方法采用半自动 96 孔蛋白沉淀，使用 ACQUITY™ UPLC BEH C18（2.1mm×50mm，1.7μm）柱进行梯度色谱分离。SCH 530348 的保留时间约为 1.5 分钟。该方法经过验证，可用于 1.00-1000ng/mL 浓度范围内 SCH 530348 的常规定量。基于重复质控样品的平均理论百分比的批内准确度优于 95.2%。基于重复质控样品的相对偏差百分比的批内精密度≤3.3%。SCH 530348 质控样品在人血浆中至少可稳定 3 个冻融循环，在-20°C 下冷冻至少 467 天，在室温下至少储存 7 小时。100μL 血浆等分试样的定量下限为 1.00ng/mL。
