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.

Keywords: HPLC; Inosiplex; LC/MS/MS; N,N-dimethylamino-2-propanol; Pharmacokinetics; p-Acetaminobenzoic acid.

Fig. 1

Chemical structures of (A) inosiplex, (B) amantadine (internal standard for DIP), and (C) paracetamol (internal standard for PABA).

Fig. 2

Product ions spectra of (A) DIP and (B) amantadine.

Fig. 3

Typical MRM chromatograms of DIP and IS (amantadine) in human plasma. (A) Blank plasma sample; (B) plasma sample spiked with 10.0 μg/mL DIP and 4.00 μg/mL amantadine (IS); and (C) plasma sample 4 h after an oral administration of 1.0 g inosiplex tablets to a volunteer (DIP 1.01 μg/mL and amantadine 4.00 μg/mL).

Fig. 4

Typical chromatograms of PABA and IS (paracetamol) in human plasma. (A) Drug-free plasma sample; (B) plasma sample spiked with PABA (t_R=7.7 min, C=1.00 μg/mL) and IS (paracetamol, t_R=5.5 min, C=5.00 μg/mL); and (C) plasma obtained from a volunteer at 0.5 h after oral administration of 0.5 g inosiplex with PABA (t_R=7.7 min, C=2.22 μg/mL) and IS (paracetamol, t_R=5.5 min, C=5.00 μg/mL).

Fig. 5

The mean plasma concentration–time profiles of (A) DIP and (B) PABA in healthy volunteers (n=10) after a single oral administration of 0.5, 1.0, and 2.0 g and multiple oral doses of 1.0 g inosiplex tablets.