Fully automated sample preparation procedure to measure drugs of abuse in plasma by liquid chromatography tandem mass spectrometry.

For the analysis of drugs and pharmaceutical compounds in biological matrices, extraction procedures are typically used for LC-MS/MS analysis often requiring manual steps in sample preparation. In this study, we report a fully automated extraction method carried out by a programable liquid handler directly coupled to an LC-MS/MS system for the determination of 42 components (illicit drugs and/or metabolites) (plus 20 deuterated internal standards). The acquisition was performed in positive ionization mode with up to 15 MRM transitions per compound, each with optimized collision energy (MRM spectrum mode) to enable qualitative library searching in addition to quantitation. After placing the sample tube into the system, no further intervention was necessary: automated preparation used 50 µL of blood or plasma with 3 µL of extracted sample injected for analysis. The method was validated according to the requirements of ISO 15189. The limit of detection and quantification was 1-5 ng/mL depending on the compound. Stability experiments found that historic calibration curve data files could accurately quantify for up to 1 month with less than 20% uncertainty. Comparison to a QuEChERS method was made using patient samples providing a regression correlation R2 = 0.98 between the two methods. This approach was successfully designed to support parallel sample preparation and analysis therefore significantly increasing sample throughput and reduced cycle times. Graphical abstract ᅟ.

Ethiodized oil uptake does not predict doxorubicin drug delivery after chemoembolization in VX2 liver tumors.

PURPOSE: To investigate the accuracy of ethiodized oil as an imaging marker of chemotherapy drug delivery after liver tumor chemoembolization in an animal model of hepatocellular carcinoma. MATERIALS AND METHODS: Eleven VX2 liver tumors (mean diameter, 1.9 cm ± 0.4) in six New Zealand White rabbits were treated with chemoembolization using ethiodized oil and doxorubicin emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intratumoral ethiodized oil distribution and calculate iodine content within four peripheral tumor quadrants and the tumor core at a central tumor slice (N = 55 total tumor sections). Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure doxorubicin concentration in the same tissue sections. Statistical correlation was performed between tissue iodine content and doxorubicin concentration by using linear regression. RESULTS: Chemoembolization was successfully performed in all tumors via the left or proper hepatic artery. A mean of 0.9 mL ± 0.6 ethiodized oil and 1.8 mg ± 1.2 doxorubicin were injected. CT-calculated tissue iodine content averaged 335 mg/mL ± 218. Corresponding LC-MS/MS analysis yielded a mean doxorubicin concentration of 15.8 µg/mL ± 14.3 in each sample. Although iodine content (391 mg/mL vs 112 mg/mL; P = .000) and doxorubicin concentration (18.0 µg/mL vs 7.2 µg/mL; P = .023) were significantly greater along peripheral tumor sections compared with the tumor core, no significant predictable correlation was evident between these measures (R(2) = 0.0099). CONCLUSIONS: Tissue ethiodized oil content is a poor quantitative predictor of local doxorubicin concentration after liver tumor chemoembolization. Future studies should aim to identify a better imaging marker for chemoembolization drug delivery.

Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC-MS-MS.

Because liver cancer is rarely suitable for surgery, transcatheter arterial chemoembolization (TACE) is used for palliative therapy. In this procedure, an emulsion of doxorubicin in iodized oil is injected directly into liver tumors through a catheter positioned within the artery supplying blood flow to the tumor. At present, there is limited understanding of factors affecting the delivery and dispersion of doxorubicin within treated tumors during TACE. This study addresses the development and application of an ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method for rapid confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model. Doxorubicin levels in liver tumors were measured using UHPLC-MS-MS and compared with computed tomography measured levels of iodized oil, a metric used clinically to indicate drug delivery. We found that tissue drug levels determined using UHPLC-MS-MS did not correlate with the regional iodized oil concentration (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs like doxorubicin spread throughout tumors, and that lack of iodized oil staining in portions of a tumor does not necessarily indicate inadequate therapy during TACE.

Photocrosslinking of a novel alpha,omega-unsaturated copolyamide: mass spectrometric study on model compounds with benzophenone as photoinitiator.

The aim of this work was to understand the reactions involved in the photocrosslinking processes of a alpha,omega-unsaturated copolyamide foreseen as a new UV-curable powder coating. The crosslinking reaction was photoinitiated with benzophenone. In this paper, the photochemical reaction between benzophenone and several model compounds was investigated. The model compounds contained functional groups which could be present in copolyamide. The products resulting from UV curing were identified using a combination of high-resolution mass spectrometry and MS(n) experiments. The characterization of the products allowed localization of the hydrogen abstraction by the type II photoinitiator during UV curing and, consequently, the determination of the reactive sites of the unsaturated polyamide chain which were involved in the photochemical reaction.