Determination Of Desloratadine And Pidotimod In Human Plasma By Lc-ms/ms And Its Application

Two rapid and sensitive liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods have been developed for the determination of desloratadine and pidotimod in human plasma, respectively, and have been successfully applied to evaluate the bioequivalence of different formulations containing desloratadine and pidotimod.1,Determination of desloratadine in human plasma and its applicationA sensitive and rapid liquid chromatographic-tandem mass spectrometric method for the determination of desloratadine in human plasma has been developed, and has been applied to evaluate the bioequivalence of two formulations of desloratadine. Followed by liquid-liquid extraction from 200μL plasma sample, chromatographic separation was performed on a Diamonsil C₁₈ column with the mobile phase of methanol-2mmol/L ammonium acetate-formic acid (75 : 25 : 0.05, v/v/v). Electrospray ionization (ESI) source was used and operated in the positive ion mode by selected reaction monitoring (SRM) mode with the transitions of m/z 311→m/z 259 and m/z 256→m/z 167 to quantify desloratadine and the internal standard, respectively. The linear range of desloratadine in human plasma was 0.1-20.0 ng/mL, LLOQ was 0.1 ng/mL. The intra-day RSD at three QC levels were 10.0%, 7.1% and 7.7%, respectively, and the inter-day RSD were 1.2%, 2.2% and 5.2%, respectively. Accuracy was within 97.5%-100.0%. The extraction recovery of desloratadine was more than 62.9%.The method was used to determine desloratadine in human plasma after an oral administration of orally disintegrating tablets containing 10 mg desloratadine (Test formulation) and common tablets of desloratadine (Reference formulation) containing 10 mg desloratadine to 18 healthy volunteers. The main pharmacokinetic parameters calculated by 3P97 programs were as follow: T_max were (2.9±0.6) and (2.8±0.6) h, C_max were (4.85±2.12) and (5.02±2.22) ng/mL, t_1/2 were (26.27±17.19) and (23.16±6.15) h, AUC_0→t were (59.1±29.6) and (57.9±26.2) ng·h/mL, AUC_0-∞ were (63.8±29.0) and (62.3±26.3) ng·h/mL, respectively. The relative bioavailability of test formulation of desloratadine was (103.4±31.8) %. According to the results of statistical analysis, the test and reference formulations of desloratadine are bioequivalent.2,Determination of pidotimod in human plasma and its applicationA sensitive and rapid liquid chromatographic-tandem mass spectrometric method for the determination of pidotimod in human plasma has been developed, and has been applied to evaluate the bioequivalence of two formulations of pidotimod. Followed by protein precipitation from 50μL plasma sample, chromatographic separation was performed on a Zirchrom Kromasil C₁₈ column with the mobile phase of acetonitrile-water-formic acid (20 : 80 : 0.5, v/v/v). Atmospheric pressure chemical ionization (APCI) source was used and operated in the positive ion mode by selected reaction monitoring (SRM) mode with the transitions of m/z 245→m/z 134 and m/z 180→m/z 72 to quantify pidotimod and the internal standard, respectively. The linear range of pidotimod in human plasma was 40.0-8000 ng/mL, LLOQ was 40.0 ng/mL. The intra-day RSD at three QC levels were 8.9%, 7.5% and 10.7%, respectively, and the inter-day RSD were 14.9%, 9.1% and 14.5%, respectively. Accuracy was within 96.8%-99.0%. The extraction recovery of pidotimod was more than 67.8%.The method was used to determine pidotimod in human plasma after an oral administration of dispersible tablets containing 800 mg pidotimod (Test formulation) and common tablets of pidotimod (Reference formulation) containing 800 mg pidotimod to 18 healthy volunteers. The main pharmacokinetic parameters calculated by 3P97 programs were as follow: T_max were (2.5±1.0) and (2.7±1.2) h, C_max were (3211±1701) and (3422±1785) ng/mL, t_1/2 were (1.6±0.4) and (1.7±0.5) h, AUC_0→t were (13412±6743) and (14703±8370) ng·h/mL, AUC_{0→∞} were (13630±6799) and (15004±8342) ng·h/mL, respectively. The relative bioavailability of test formulation of pidotimod was (98.2±26.8) %. According to the results of statistical analysis, the test and reference formulations of pidotimod are bioequivalent.