Pharmacokinetic study of inosiplex tablets in healthy Chinese volunteers by hyphenated HPLC and tandem MS techniques

Abstract

Inosiplex is a compound formulation composed of inosine and p-acetaminobenzoic acid (PABA) salt of N,N-dimethylamino-2-propanol (DIP). This study was to investigate the clinical plasma pharmacokinetic properties of DIP and PABA after single and multiple oral doses of inosiplex tablets in healthy Chinese volunteers. The established LC/MS/MS method for plasma DIP determination had a linear range of 0.02–10 µg/mL, and the HPLC method for plasma PABA determination had a linear range of 0.05–40 µg/mL. Linear pharmacokinetic characteristics were found with single oral doses of 0.5, 1.0 and 2.0 g. No obvious accumulation effects were observed for DIP and PABA.

Development, Validation, and Application of the LC-MS/MS Method for Determination of 4-Acetamidobenzoic Acid in Pharmacokinetic Pilot Studies in Pigs

“…A 150 × 3 mm Atlantis T3 analytical column with a 3 µm particle size was used in the analyses; however, a 150 × 3 mm XBridge column with a 3.5 µm particle size was also suitable for studying these analytes ( Supplementary Figure S1 ). The method developed by Chen et al 2013 for PAcBA analysis employed a universal C18 column, with a diameter and particle size much larger than those in the column used in this experiment [ 11 ]. Moreover, the Atlantis T3 column retains polar compounds better than the C18 column, which is why the former was considered a better option.…”

“…The best result was achieved with a ratio of 99:1 v/v when the gradient started with the column temperature set at 20 °C ( Table 1 ). For comparison, Chen et al, 2013 used a mobile phase composed of methanol—0.2% ammonium acetate and a 0.2% acetic acid solution at a ratio of 15:85 v/v [ 11 ]. We rejected the use of methanol due to maximal reduction of the baseline during analysis.…”

“…The preparation of a sample for analysis is the main element in the development of a new analytical method for a given compound because, to ensure reproducibility, the validation of the whole method focuses mainly on the way the sample is prepared [ 12 , 13 ]. In the literature, only one publication by Chen et al, 2013 could be found regarding the preparation of the matrix, which was plasma (for the extraction of PAcBA) [ 11 ]; thus, it was decided to develop a new method for the preparation of plasma samples for the determination of PAcBA. As the main goal was to obtain a quick, easy, short, sensitive, and low-cost method of plasma purification, it was decided to use the liquid–liquid extraction (LLE) technique despite its disadvantages.…”

“…Additionally, due to the fact that Inosine Pranobex consists of three different components, the PK has to be determined for each component. So far, the PK of PAcBA has only been examined in humans [ 9 , 10 , 11 ]. That study did not account for a potential matrix effect, and it used HPLC with UV light detection, which is less sensitive than tandem mass spectrometry.…”

Development of an LC−MS/MS method for determination of 2-oxo-clopidogrel in human plasma

“…However, the high activity of thiolactone poses great challenge for the establishment of analytic method. For the lucubration of clopidogrel metabolism and individual treatment, this study focused on developing an LC−MS/MS method [18] , [19] to determine the concentration of 2-oxo-clopidogrel. To achieve the goal, the method was validated and applied to a pharmacokinetic study.…”