Liquid chromatographic method for irinotecan estimation: Screening of p-gp modulators

Abstract

Tariq, et al.: LC Method for Screeing of P-gp ModulatorsThe present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for the estimation of irinotecan in the physiological media in order to assess the permeability profile of irinotecan, using the everted gut sac, in the presence of various P-gp modulators. Separation was achieved using, C18 column with mobile phase consisting of acetonitrile and 0.045 µM sodium dihydrogen phosphate dihydrate buffer containing ion pair agent heptane sulphonic acid sodium salt (0.0054 µM), pH 3. The flow rate was maintained at 1 ml/min and analysis was performed at 254.9 nm using PDA detector. Calibration data showed an excellent linear relationship between peak-area verses drug concentration (r 2 , 0.9999). Linearity was found to be in the range of 0.060-10.0 µg/ml. Limits of detection and quantification were found to ~0.020 µg/ml and ~0.060 µg/ml, respectively. The developed method was found to be precise (RSD <1.5%, for repeatability and <2.55% for intermediate precision, acceptable ranges of precision), accurate (The recovered content of irinotecan in the presence of various P-gp modulators varied from 96.11-101.51%, within acceptable range, 80-120%), specific and robust (% RSD <2). Developed method has been applied successfully for the evaluation of eleven P-gp modulators from diverse chemical class.

Irinotecan-Review of Analytical Methods Developed for Pharmaceutical Dosage Forms and Biological Fluids

“…IRI has made important contributions to the treatment of solid tumours all around the world for more than two decades [4]. It is a therapy for colorectal and small cell lung cancer that has been approved by the United States-Food and Drug Act (US-FDA) [3,5]. Chemically, IRI is a Camptothecin analogue, available with trade names CAMPTOSAR, IRINOMIL, IRNOCAM, TORSIRIN, IRINOTEL, IRBEST [1][2][3][4][5][6].…”

“…It is a therapy for colorectal and small cell lung cancer that has been approved by the United States-Food and Drug Act (US-FDA) [3,5]. Chemically, IRI is a Camptothecin analogue, available with trade names CAMPTOSAR, IRINOMIL, IRNOCAM, TORSIRIN, IRINOTEL, IRBEST [1][2][3][4][5][6]. Its molecular formula is C33H38N4O6, molecular weight is 586.7 g/mol, available in solid state as pale yellow color powder.…”

“…Both of these molecules exist in two states at the same time: a lactone form that is active and a carboxylate form that is inactive with no inhibitory activity against topoisomerase I. At lower pH, lactone forms predominate, whereas carboxylate forms predominate at above pH 8 [5]. As IRI exhibits cytotoxic activity, it is employed in the cure of different types of cancers.…”

An analytical “quality by design” approach in RP-HPLC method development and validation for reliable and rapid estimation of irinotecan in an injectable formulation

“…Apart from the economical setback of using fluorescent detectors, IRI exhibits a difference in fluorescence depending on the acidity or basicity of the medium (11). Prior literature confirmed the availability of few methods for quantification of IRI using HPLC with a UV detector (12)(13)(14). Although few methods are available for the estimation of IRI in the analytical and/or bioanalytical samples, still there is a need to work on the method sensitivity, robustness and analysis cost.…”