Stereoselectivity of the Excretion of R-/S-HPABA in Rats
- VernacularTitle: R-/S-HPABA大鼠体内排泄规律的立体选择性
- Author:
Can-Ming WANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Chiral drug; Excretion; R-/S-HPABA; Stereoselectivity; UHPLC-MS/MS
- From: Chinese Pharmaceutical Journal 2020;55(12):1034-1041
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To develop an UHPLC-MS/MS method for the determination of R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA) in rat urine, feces and bile and apply the method to study the excretion of R-/S-HPABA in rats. METHODS: After liquid-liquid extraction by ethyl acetate,the separation was achieved on a Thermo Syncronis C18 column (2.1 mm×50 mm, 1.7 μm) using mobile phase consisting of solvent A (methanol) and solvent B (0.1% formic acid) at a flow rate of 0.4 mL•min-1. The concentration of R-/S-HPABA after single dose oral administration of 50 mg•kg-1 R-/S-HPABA to rats was detected by UHPLC-MS/MS method. RESULTS: The calibration curve was linear over the range of 0.002-5 μg•mL-1 and the lower limit of quantification (LLOQ) was 0.002 μg•mL-1. The intra-and inter-day RSDs were less than 13.0% and the accuracy (relative error) of R-/S-HPABA was within -7.5%-4.2%. The average recoveries were (87.3±3.4)%-(104.4±7.0)%. After intragastric administration of R-HPABA and S-HPABA at a dose of 50 mg•kg-1, the cumulative amounts of R-HPABA and S-HPABA excreted in the urine (0-48 h) were (536.1±29.7) and (771.7±38.6) μg, the urinary excretion amounted to 4.9% and 7.0% of the dosage, respectively; the cumulative amounts of R-HPABA and S-HPABA excreted in feces (0-48 h) were (3 963.0±345.2) and (4 771.8±355.0) μg, the fecal excretion amounted to 36.0% and 43.4% of the dosage, respectively; the cumulative amounts of R-HPABA and S-HPABA excreted in bile (0-12 h) were (150.6±30.3) and (747.7±89.2) μg, the biliary excretion amounted to 1.4% and 6.8% of the dosage, respectively; the summation of urinary, fecal and biliary excretion amounted to 42.3% and 57.2% of the dosage in rats for R-HPABA and S-HPABA, respectively. The cumulative amounts of S-HPABA excreted in the urine, feces and bile were higher than those of R-HPABA. CONCLUSION: This UHPLC-MS/MS method is suitable for the study of the excretion of R-/S-HPABA in rats. The excretion of the two enantiomers in rats shows significant stereoselectivity difference.
