Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.
Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.
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DOI：
10.1016/j.jpba.2022.114685
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发表时间：
2022-05-10
影响因子：
3.4
通讯作者：
Figg WD
中科院分区：
文献类型：
--
作者：
Goodell JC;Zimmerman SM;Peer CJ;Prabhu V;Yin T;Richardson WJ;Azinfar A;Dunn JA;Mullin M;Theeler BJ;Gilbert M;Figg WD
ONC206是一种正在临床上作为单一药物在第一次人体试验中口服的咪普利酮衍生物(NCT04541082)。这项正在进行的临床试验需要对ONC206进行药代动力学分析，以充分描述其药理特征。目前还没有已发表的ONC206定量的生物分析方法。为了解ONC206的临床药代动力学，建立了一种灵敏、简便的人血浆中ONC206的UHPLC-MS/MS测定方法。蛋白质沉淀法可以快速、灵敏地测定人血浆中的ONC206。采用Phenomeex Kinetex C18(50 mm×2.1 mm，1.3 mm，100 mm)分析柱，ONC206和内标[2H]7-ONC206的色谱峰对称、锐利，通过多反应监测进行检测。方法的校正范围为1~500ngmL，线性回归模型(R2>；0.99732±0.0010)拟合最好。该方法准确度高(<；±0.9%偏差)，精密度(<；11%变异系数)，选择性好，专属性强，无干扰，批间矩阵变异小。ONC206在溶液和人血浆中表现出良好的短期、长期和多次冻融循环稳定性。这一完全有效的方法被用来量化在NCI参加上述临床试验的患者的ONC206血浆浓度，以证明其临床适用性。
ONC206 is an imipridone derivative that is being developed clinically as a single agent given orally in a first-in-human trial (NCT04541082). This ongoing clinical trial requires pharmacokinetic analysis of ONC206 to fully characterize its pharmacologic profile. There is currently no published bioanalytical method for ONC206 quantitation. To understand the clinical pharmacokinetics of ONC206, a sensitive yet simple uHPLC–MS/MS method for quantitation of ONC206 in human plasma was developed. Protein-precipitation allowed rapid and sensitive bioanalytical measurement of ONC206 in human plasma. A Phenomenex Kinetex C18 (50 ×2.1 mm, 1.3 µm, 100 Å) analytical column achieved symmetrical and sharp chromatography peaks of ONC206 and the internal standard, [2H]7-ONC206, which were detected using multiple reaction monitoring. The assay calibration range was 1–500 ng/mL and was best fit by a linear regression model (r2> 0.99732 ± 0.0010). The method proved accurate (< ± 9% deviation), precise (<11%CV), selective and specific with no interference and low inter-lot matrix variability. ONC206 demonstrated excellent short-term, long-term, and multiple freeze-thaw cycle stability in solution and human plasma. This fully validated method was used to quantitate ONC206 plasma concentrations from patients enrolled in the aforementioned clinical trial at the NCI to demonstrate its clinical applicability.
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影响因子：
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作者：
Wagner, Jessica;Kline, Christina Leah;El-Deiry, Wafik S.
通讯作者：
El-Deiry, Wafik S.
影响因子：
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4
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通讯作者：
Graves, Lee M.
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影响因子：
37.3
作者：
Allen JE;Krigsfeld G;Patel L;Mayes PA;Dicker DT;Wu GS;El-Deiry WS
通讯作者：
El-Deiry WS