Development and Validation of a Liquid Chromatography Mass Spectrometry Method for the Determination of Zileuton in Human Plasma

Abstract

A selective and sensitive liquid chromatography-tandem mass spectrometric method (LC-MS/MS) has been developed and validated for the quantification of zileuton in human plasma. Deuterated internal standard (zileuton D4) was used as the internal standard (ISTD). Zileuton was extracted by liquid-liquid extraction using methyl tert-butyl ether and separated by isocratic elution on a C18 column (100 × 4.6 mm, 5 μm, Discovery C18) with the mobile phase consisting of 1 mM ammonium acetate buffer and methanol in the ratio of 10:90. A flow rate of 1.0 ml/min was used with isocratic elution. Multiple reaction monitoring transitions in positive mode for zileuton and the internal standard were 237.3/161.2 and 241.2/161.1, respectively. The method was validated within the linearity range of 50.5–10,012.7 ng/ml for the bioanalytical method validation parameters like selectivity, accuracy, precision, recovery, stability, and matrix effect.

Evaluation of gender differences in the pharmacokinetics of oral zileuton nanocrystalline formulation using a rat model

“…Stock solutions of zileuton API were prepared in methanol at a concentration of 4 mg/mL. The control samples (plasma, urine and ileal tissue homogenate) were spiked with zileuton stock solution to obtain concentration ranges from 125 to 16,000 ng/mL and underwent identical extraction procedures with some modifications as described previously ( Prakash et al, 2014 ). The calibration curves were constructed for each biological matrix by plotting peak area of zileuton versus the spiked concentration of standards.…”

“…Zileuton was extracted from plasma and urine using the method described by Prakash et al ( Prakash et al, 2014 ). Intestinal ileal tissue was homogenized as described by Gokulan et al, with some modifications ( Gokulan et al, 2018 ) as described below.…”

Rp-HPLC Method for the Estimation of Zileuton in Tablet Formulation

“…It is advised that the doses of each medication be monitored and/or reduced accordingly. Literature survey reveals analytical methods reported for estimation of zileuton in API, pharmaceutical dosage form and biological fluid includes spectrophotometry [3], [4], [5], [6], [7], [8], [9], [10], RP-HPLC [11], [12], [13] and LC-MS [14], [15]. Obviously, HPLC methods [16], [17] are superior in compared to RP-HPLC Method for The Estimation of Zileuton In Tablet Formulation spectrophotometric methods in terms of accuracy and sensitivity.…”

Quantitative Determination of Zileuton from Spiked Human Plasma Using Liquid-Liquid Extraction Followed by RP-HPLC and UV Analysis

“…Zileuton reduces these symptoms through its specific inhibitory activity. 17,18 Patients consuming the recommended dose of 600 mg of zileuton exhibited a peak plasma concentration of 4.41 mg/L. 19 Numerous analytical techniques are reported in the literature for the quantitative estimation of zileuton.…”