Development and Validation of Amisulpride in Human Plasma by HPLC Coupled with Tandem Mass Spectrometry and its Application to a Pharmacokinetic Study

In this study, authors developed a simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for quantification of Amisulpride in human plasma using Amisulpride-d5 as an internal standard (IS). Chromatographic separation was performed on Zorbax Bonus-RP C18, 4.6 × 75 mm, 3.5 μm column with an isocratic mobile phase composed of 0.2% formic acid:methanol (35:65 v/v), at a flow-rate of 0.5 mL/min. Amisulpride, Amisulpride-d5 was detected at m/z 370.1→242.1 and 375.1→242.1. The drug and the IS were extracted by a liquid-liquid extraction method. The method was validated over a linear concentration range of 2.0–2500.0 ng/mL for Amisulpride with a correlation coefficient of (r2) ≥ 0.9982. This method demonstrated intra- and inter-day precision within 0.9 to 1.7 and 1.5 to 2.8 % and intra- and inter-day accuracy within 98.3 to 101.5 and 96.0 to 101.0 % for Amisulpride. Amisulpride was found to be stable at 3 freeze–thaw cycles, bench top and auto sampler stability studies. The developed method was successfully applied to a pharmacokinetic study

Bioanalytical method development and validation of milnacipran in rat plasma by LCâMS/MS detection and its application to a pharmacokinetic study

A simple, sensitive and specific liquid chromatographyâtandem mass spectrometry (LCâMS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquidâliquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6 mmÃ75 mm, 3.5 µm) column with an isocratic mobile phase composed of 10 mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7 mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2â230.3 and m/z 257.2â240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00â400.00 ng/mL with a correlation coefficient (r2)â¥0.9850. This method demonstrated intra- and inter-day precision within 5.40â10.85% and 4.40â8.29% and accuracy within 97.00â104.20% and 101.64â106.23%. MC was found to be stable throughout three freezeâthaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration. Keywords: Milnacipran, Pharmacokinetics, Rat plasma, LCâMS/M