Bioanalytical technique for determination of tasimelteon in human plasma by LC–MS/MS and its application to pharmacokinetic study in humans

A highly sensitive, specific and rapid liquid chromatography–tandem mass spectrometry technique for the quantification of tasimelteon in human plasma has been developed and validated using tasimelteon‐d₅ as internal standard. Liquid–liquid extraction technique with ethyl acetate was used for extraction of tasimelteon from the plasma. The chromatographic separation was achieved on an Agilent Zorbax, Eclipse, C₁₈ (4.6 × 50 mm, 5 μm) column using a mobile phase of acetonitrile and 0.02% formic acid buffer (85:15, v/v) with a flow rate of 0.5 mL/min. A detailed method validation was performed as per the United States Food and Drug Administration guidelines. The linear calibration curve was obtained over the concentration range 0.30–299 ng/mL. The API‐4000 liquid chromatography–tandem mass spectrometry was operated under multiple reaction monitoring mode during analysis. The validated method was successfully applied to estimate plasma concentration of tasimelteon after oral administration of a single dose of a 20 mg capsule in healthy volunteers under fasting conditions. The maximum concentration of the drug achieved in the plasma was 314 ± 147 ng/mL and the time at which this concentration was attained was 0.54 ± 0.22 h.     

Antibody drug conjugates: Development,characterization, and regulatory considerations

Previously, cancer chemotherapy was often accompanied by severe side effects. Antibody drug conjugates (ADCs) were introduced to address this treatment complication. ADCs are a potent category of bioconjugates and immunoconjugates designed as targeted therapy for the treatment of cancer. ADCs are complex molecules composed of an antibody linked via linker chemistry to a cytotoxic payload or drug. Therefore, biologic properties of the cell‐surface target antigen are important in designing an effective ADC as an anticancer agent. ADCs have the ability to discriminate between the healthy and diseased tissue, so that healthy cells are less effected and get maximum therapeutic benefit. This review describes the development, characterization, and regulatory consideration of ADCs, and it summarizes the approved products in the market and in clinical trials.