New UPLC-MS/MS assay for the determination of tamoxifen and its metabolites in human plasma, application to patients.

AIM: A rapid UPLC-MS/MS method for the determination of tamoxifen (TAM), N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in human plasma was validated, after a simple protein precipitation. MATERIALS AND METHODS: The analysis was achieved on a C18 analytical column, using a gradient elution with a mobile phase of water and acetonitrile for 4.5 min. RESULTS: The validated method demonstrated good linearity between 1 and 500 ng/ml for TAM and N-desmethyltamoxifen; between 0.2 and 100 ng/ml for endoxifen and between 0.1 and 50 ng/ml for 4-hydroxytamoxifen. The method also provided satisfactory results in terms of within day and between day imprecisions and accuracy, and also in terms of time stability and specificity. CONCLUSION: The method is applied routinely for TAM monitoring from patients undergoing therapy.

A new, validated wipe-sampling procedure coupled to LC-MS analysis for the simultaneous determination of 5-fluorouracil, doxorubicin and cyclophosphamide in surface contamination.

A wipe-sampling procedure followed by a simple liquid chromatography-mass spectrometry method was developed and validated for the simultaneous quantification of three cytotoxic drugs [5-fluorouracil (5FU), doxorubicin and cyclophosphamide (CP)] for the determination of surface contamination. After a solid-phase extraction procedure with wiping filter paper, the separation was performed within 30 min using a gradient mobile phase. The method was validated according to the recommendations of the US Food and Drug Administration. Wiping was performed using Whatman(®) filter paper on different surfaces such as stainless steel, polypropylene and glass. The method was linear, between 10 and 500 ng per wiping sample (i.e., 0.1-5 ng/cm(2)) for 5FU and doxorubicin, and between 1-100 ng per wiping sample (i.e., 0.01-1 ng/cm(2)) for CP. The lower limits of detection and quantification were 5 and 10 ng per wiping sample for 5FU and doxorubicin, and 0.5 and 1 ng per wiping sample for CP. This new sensitive methodology for surface contamination studies was successfully applied on commercial vials and different places in a cancer research hospital. This approach is particularly suitable to assess the risk of occupational exposure to cytotoxic drugs and to optimize the cleaning process, especially for the most toxic molecule studied, CP.

A new rapid and sensitive LC-MS assay for the determination of sorafenib in plasma: application to a patient undergoing hemodialysis.

A simple liquid chromatography-mass spectrometry method was developed and validated for quantification of sorafenib (Nexavar) in human plasma. After a solid-phase extraction procedure, the separation was performed within 2 minutes using an isocratic flow of a mobile phase consisting of formic acid/acetonitrile applied on a C18 analytical column. The analyte was detected by mass spectrometry in the single-ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r² > 0.99) between 10 and 10,000 ng/mL. The lower limits of detection and quantification were 5 and 10 ng/mL, respectively. Within-day and between-day imprecisions were less than 10.4%, and inaccuracy did not exceed 8.7%. The mean extraction recovery was 92.2%. The method also provided satisfactory results in terms of time stability and dilution integrity. Sorafenib plasma concentrations of the studied patient ranged between 1831 and 3459 ng/mL. This new technique is rapid, sensitive, and was applied to the determination of sorafenib plasma concentrations in a patient undergoing hemodialysis. Our results indicate that sorafenib is not cleared from plasma by hemodialysis, although analysis should be delayed after dialysis to avoid erratic fluctuations.