Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa 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.

Precision targeting of liver lesions with a needle-based soft tissue navigation system.

In this study, we assessed the targeting precision of a previously reported needle-based soft tissue navigation system. For this purpose, we implanted 10 2-ml agar nodules into three pig livers as tumor models, and two of the authors used the navigation system to target the center of gravity of each nodule. In order to obtain a realistic setting, we mounted the livers onto a respiratory liver motion simulator that models the human body. For each targeting procedure, we simulated the liver biopsy workflow, consisting of four steps: preparation, trajectory planning, registration, and navigation. The lesions were successfully hit in all 20 trials. The final distance between the applicator tip and the center of gravity of the lesion was determined from control computed tomography (CT) scans and was 3.5 +/- 1.1 mm on average. Robust targeting precision of this order of magnitude would significantly improve the clinical treatment standard for various CT-guided minimally invasive interventions in the liver.