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.

Simultaneous quantification of lidocaine and prilocaine in human plasma by LC-MS/MS and its application in a human pharmacokinetic study.

OBJECTIVE: The aim of the work was to develop and validate a simple, sensitive and selective Liquid chromatography with Mass spectroscopic method for simultaneous quantification of lidocaine and prilocaine in human plasma. DESIGN AND METHODS: Analytes and the internal standards from human plasma were extracted by using solid- phase extraction technique using Waters Oasis® HLB 1 â€‹cc (30 â€‹mg) cartridges. The reconstituted samples were chromatographed on Phenomenex Kinetex EVO 4.6*100 â€‹mm 2.6 µ 100A column by using a mixture of acetonitrile and 5 â€‹mM ammonium acetate buffer (80:20, v/v) as the mobile phase at a flow rate of 0.6 â€‹mL/min. RESULTS: The method was validated over the concentration range of 0.10-201.80 ng/mL for lidocaine and 0.10-201.66 ng/mL for prilocaine. The calibration curve obtained was linear. CONCLUSION: Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 3.0 min for each sample, make it possible to analyze more than 350 human plasma samples per day. The proposed method was found applicable for pharmacokinetic studies.