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 separa...

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Main Authors: Kanchanamala Kanala (Author), Nagiat T. Hwisa (Author), Babu Rao Chandu (Author), Prakash Katakam (Author), Mukkanti Khagga (Author), B.R. Challa (Author), Bhavyasri Khagga (Author)
Format: Book
Published: Elsevier, 2013-12-01T00:00:00Z.
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Summary: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/MS
Item Description:2095-1779
10.1016/j.jpha.2013.03.009