Department of General, Visceral and Vascular Surgery, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.
Research Programme "Clinician Scientist Programme", Interdisciplinary Center of Clinical Research, Medical Faculty Jena, Jena University Hospital, Friedrich Schiller University Jena, Salvador-Allende-Platz 29, 07747 Jena, Germany.
Int J Mol Sci. 2023 Nov 17;24(22):16431. doi: 10.3390/ijms242216431.
Thymoquinone (TQ) is the primary component of L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.
姜酮（TQ）是 L.（NS）油的主要成分，因其具有抗氧化、抗纤维化、抗炎、抗癌以及抗凋亡和促凋亡特性，而被认为具有很强的肝保护作用。本工作旨在建立一种血清中 TQ 的测定方法，以便在靶向治疗应用之前研究 TQ 的药代动力学。在第一步中，根据欧洲药品管理局（EMA）的标准，建立并验证了一种用于检测和定量油基质中 TQ 的气相色谱-质谱法。为了评估临床应用，测定了 19 种油制剂中的 TQ 浓度。其次，向两种血清样品中加入 TQ，然后用甲苯沉淀蛋白后测定 TQ 浓度。第三，一名健康志愿者在口服高浓度 NS 油 30 和 60 分钟后分别采集 1 克和 3 克，用于测定血清 TQ 水平。成功建立和验证了测量方法后，在瓶装 NS 油产品（No.1）中发现了最高浓度的 TQ（36.56μg/L）。由于胶囊更适合口服，因此使用 TQ 浓度第三高的产品（No.3：24.39μg/L）进行了所有进一步的测试。在加入 TQ 的血清样品中，TQ 浓度在 5 至 10μg/mL 范围内可靠检测到。然而，口服 NS 油（No.3）后，人血清中未检测到 TQ 和/或其衍生物。在血清中加入 TQ 或口服后检测到 TQ 的差异可能归因于 TQ 在生物基质中的不稳定性以及其与蛋白质的强结合特性。因此，药代动力学研究不可行。在动物模型中进行同位素标记 TQ 的研究对于使用替代模式研究 TQ 的药代动力学是必要的。
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