Metabolism Analysis

Determination of the active compound against multi-resistant tuberculosis macozinone (PBTZ 169) concentration in rat plasma by UPLC-MS/MS method and its pharmacokinetics*

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  • Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051, China

Revised date: 2022-11-14

  Online published: 2024-06-24

Abstract

Objective: To establish a rapid and accurate method of UPLC-MS/MS for the determination of macozinone(PBTZ 169) concentration, a novel active compound against multi-resistant tuberculosis, in rat plasma and to study its pharmacokinetics in rats. Methods: Carbamazepine was used as internal standard. After the protein was precipitated by acetonitrile, the plasma samples were separated on the XBridge BEH C18(100 mm×2.1 mm, 2.5 μm) chromatographic column through gradient elution by acetonitrile and 0.1% formic acid as mobile phase. The flow rate was 0.5 mL·min-1 and sample volume was 10 μL. Then the analytes were detected by the electrospray ionization (ESI) sourcein with positive ion scanning. The detection conditions of PBTZ 169 and internal standard(carbamazepine) by mass spectrometry were m/z 457.2→344.1 and m/z 237.2→194.2, respectively. After the rats were given 20 mg·kg-1 PBTZ 169 and the plasma concentration of PBTZ 169 was detected at different time points. The pharmacokinetic parameters were calculated and statistically analyzed. Results: The mass concentration of PBTZ 169 had a good linear relationship between 0.7 and 740.0 ng·mL-1(r=0.996 0). The extraction recovery of PBTZ 169 and internal standard were between 99.5% and 110.2% and the RSDs of intra day and inter day were ranged from 1.3% to 4.2%. PBTZ 169 plasma samples were placed at room temperature for 6 h, the automatic sampler was placed for 24 h after the blood sample was processed, refrigerated at -70 ℃ for 15 d and repeatedly freeze-thaw at -70 ℃ for 3 times. Finally, the RSDs were all lower than 15%. After oral intragastric administration of PBTZ 169 to rats, the main pharmacokinetic parameters of PBTZ 169 in rats were as follows: Cmax was (374.8±116.3) ng·mL-1, Tmax was (0.8±0.1) h, AUC0~∞ was (1 180.0±383.5) ng·h·mL-1, T1/2 was (3.7±0.7) h, MRT0~∞ was (4.7±1.2) h. Conclusion: This method is simple, rapid, sensitive and suitable for pharmacokinetic study of PBTZ 169.

Cite this article

ZHI Xu-ran, XING Xiao-qing, LI Ying, LIU Hong-tao . Determination of the active compound against multi-resistant tuberculosis macozinone (PBTZ 169) concentration in rat plasma by UPLC-MS/MS method and its pharmacokinetics*[J]. Chinese Journal of Pharmaceutical Analysis, 2023 , 43(1) : 126 -132 . DOI: 10.16155/j.0254-1793.2023.01.15

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