Liquid chromatography/tandem mass spectrometry method for quantitative estimation of solutol HS15 and its applications

Abstract

A rapid, sensitive and selective pseudoMRM (pMRM)-based method for the determination of solutol HS15 (SHS15) in rat plasma was developed using liquid chromatography/tandem mass spectrometry (LC–MS/MS). The most abundant ions corresponding to SHS15 free polyethyleneglycol (PEG) oligomers at m/z 481, 525, 569, 613, 657, 701, 745, 789, 833, 877, 921 and 965 were selected for pMRM in electrospray mode of ionization. Purity of the lipophilic and hydrophilic components of SHS15 was estimated using evaporative light scattering detector (ELSD). Plasma concentrations of SHS15 were measured after oral administration at 2.50 g/kg dose and intravenous administration at 1.00 g/kg dose in male Sprague Dawley rats. SHS15 has poor oral bioavailability of 13.74% in rats. Differences in pharmacokinetics of oligomers were studied. A novel proposal was conveyed to the scientific community, where formulation excipient could be analyzed as a qualifier in the analysis of new chemical entities (NCEs) to address the spiky plasma concentration profiles.

Mass Spectrometry as a Workhorse for Preclinical Drug Discovery: Special Emphasis on Drug Metabolism and Pharmacokinetics

“…This in turn can be instrumental in causing matrix effects, thereby questioning the reliability of preclinical PK parameters. This phenomenon has been reported by us in the past for various excipients such as PEG 400 [110,116,117], Cremophor EL [111,118] and Solutol HS15 [112,119].…”

“…Reduction of matrix effects can be achieved through various strategies including decreasing the level of matrix components, improving chromatographic separation of interfering materials from the analyte, various sample preparation strategies, lower injection volumes, and even by simple dilution of samples to reduce the overall concentrations of both analyte and co-extracted materials [126,127]. Switching ionization sources will also help in mitigating the matrix effects [112,116,118,119]. Matrix effects occurring in the early time point samples can be monitored, using another aliquot of the early time point samples analyzed at a higher dilution [128].…”

Three-dimensional aspects of formulation excipients in drug discovery: a critical assessment on orphan excipients, matrix effects and drug interactions

“…This in turn can be instrumental in causing matrix effects, thereby weakening the reliability of preclinical pharmacokinetic parameters. This phenomenon has been reported by us for various excipients such as PEG400, cremophor EL and solutol HS15 [ [58] , [59] , [60] , [69] , [70] , [71] , [72] ]. Formulation vehicles could cause 80%–90% ion suppression when administered in both oral and intravenous administration routes [ 63 , 64 , 73 , 74 ].…”

Quantification of the actual composition of polymeric nanocapsules: a quality control analysis

“…On other occasions, the molecule of interest may be labile and, consequently, be fragmented in the ESI source. This was the case for macrogol 15-hydroxystearate, where an in-source fragment of m/z 309.3 was detected [ 23 ]. Since this fragment could not be further fragmented in the collision cell, it was necessary to perform a pseudoMRM transition ( m/z 309.3 → 309.3).…”