LC-MS/MS assay for the determination of natamycin in rabbit and human plasma: Application to a pharmacokinetics and protein binding study

Yashpal Singh Chhonker; Devendra Kumar; Pankaj Shrivastava; Deepak Kumar; Rajbir Singh; Hardik Chandasana; Rabi Sankar Bhatta

doi:10.1016/j.jpha.2012.11.003

LC-MS/MS assay for the determination of natamycin in rabbit and human plasma: Application to a pharmacokinetics and protein binding study

J Pharm Anal. 2013 Apr;3(2):144-148. doi: 10.1016/j.jpha.2012.11.003. Epub 2012 Dec 12.

Authors

Yashpal Singh Chhonker¹, Devendra Kumar¹, Pankaj Shrivastava¹, Deepak Kumar¹, Rajbir Singh¹, Hardik Chandasana¹, Rabi Sankar Bhatta¹

Affiliation

¹ CSIR-Central Drug Research Institute, Pharmacokinetics and Metabolism Division, Lucknow, UP 226001, India.

Abstract

To enable reliable quantification of natamycin in rabbit and human plasma, a validated, sensitive and selective liquid chromatography-tandem mass spectrometry assay was developed. The chromatographic separation was achieved isocratically on a Cyano column using methanol: aqueous 3.5 mM ammonium acetate (pH 4) (90:10 v/v). The assay was validated over a concentration range of 6.25-400 ng/mL with lower limit of detection of 3.12 ng/mL. Quantification was performed using the transitions 664.5→137.2m/z for natamycin and 923.5→183.4m/z for the IS. The method was validated with respect to linearity, accuracy, precision, recovery and stability. This assay has been successfully applied to a pharmacokinetic study of natamycin in NZ rabbit and plasma protein binding in human plasma.

Keywords: LC–MS/MS; Natamycin; Pharmacokinetics; Protein binding.