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基于 HPLC-MS/MS 的人血浆中德瓦鲁单抗定量分析:方法建立与绿色评估

Fast and Sensitive Bioanalytical Method for the Determination of Deucravacitinib in Human Plasma Using HPLC-MS/MS: Application and Greenness Evaluation.

机构信息

Department of Pharmaceutical Analysis, Anurag University, Venkatapur, Ghatkesar Rd., Hyderabad 500088, Telangana, India.

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.

出版信息

Molecules. 2023 Jul 17;28(14):5471. doi: 10.3390/molecules28145471.

Abstract

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to analyze DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The extract was then subjected to the chromatographic system separation using the ACE-C18 column (4.6 × 100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 /, respectively). The flow rate used was set at 0.9 mL min. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in multiple reaction monitoring (MRM) mode. The ion transitions / 426.3 → 358.2 were used for DEU quantitation, while the ion transitions / 291.1 → 261.1 were used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 and 601.050 ng/mL, utilizing a weighting factor of 1/x.

摘要

斑块型银屑病是一种常见的、持久的疾病,会影响免疫系统,对患者的身体健康、幸福感和有效工作能力产生重大负面影响。德瓦鲁单抗(DEU)是第一种用于治疗斑块型银屑病的口服药物,这是一种慢性皮肤病,会导致皮肤出现红色、鳞屑斑块。DEU 是一种称为口服 Janus 激酶(JAK)抑制剂的药物,通过阻断在银屑病相关炎症和免疫反应中发挥作用的特定酶而起作用。因此,采用了一种快速、简便、新颖、可靠、灵敏和直接的液相色谱-串联质谱(LC-MS/MS)方法来分析血浆样本中的 DEU。用于测定人血浆中 DEU 的 LC-MS/MS 方法基于使用甲氧苄啶作为内标(IS)。DEU 和 IS 的分离通过液-液萃取(LLE)进行。然后将提取物通过 ACE-C18 柱(4.6×100mm,5μm)进行色谱系统分离。所采用的流动相由甲醇和 2mM 甲酸铵溶液(80:20,分别组成。使用的流速设定为 0.9mL/min。该创新策略是通过在多重反应监测(MRM)模式下运行 AB SCIEX API 4000 质谱仪和电喷雾电离源来实现的。用于 DEU 定量的离子跃迁为 / 426.3→358.2,而用于甲氧苄啶定量的离子跃迁为 / 291.1→261.1。在验证浓度范围为 0.500 至 601.050ng/mL 时,DEU 的准确性、精密度、线性、回收率和选择性被认为是可接受的,使用的加权因子为 1/x。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54f/10384560/e702dfdc7a04/molecules-28-05471-g001.jpg

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