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  • P-ISSN2233-4203
  • E-ISSN2093-8950

Liquid Chromatography-Tandem Mass Spectrometric Analysis of Nannozinone A and Its Application to Pharmacokinetic Study in Mice

Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2021, v.12 no.1, pp.21-25
https://doi.org/10.5478/MSL.2021.12.1.000
Chul Haeng Lee (College of Pharmacy, Dankook University)
Soobin Kim (College of Pharmacy, Dankook University)
Jaehyeok Lee (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Ji-Hyeon Jeon (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Im-Sook Song
Young Taek Han (College of Pharmacy, Dankook University)
Min-Koo Choi (College of Pharmacy, Dankook University)

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Abstract

We aimed to develop and validate a sensitive analytical method of nannozinone A, active metabolite of Nannochelins A extracted from the Myxobacterium Nannocytis pusilla, in mouse plasma using a liquid chromatography-tandem mass spec-trometry (LC-MS/MS). Mouse plasma samples containing nannozinone A and 13 C-caffeine (internal standard) were extracted using a liquid-liquid extraction (LLE) method with methyl tert-butyl ether. Standard calibration curves were linear in the concen-tration range of 1 - 1000 ng/mL (r 2 > 0.998) with the inter- and intra-day accuracy and precision results less than 15%. LLE method gave results in the high and reproducible extraction recovery in the range of 78.00–81.08% with limited matrix effect in the range of 70.56-96.49%. The pharmacokinetics of nannozinone A after intravenous injection (5 mg/kg) and oral administra- tion (30 mg/kg) of nannozinone A were investigated using the validated LC-MS/MS analysis of nannozinone A. The absolute oral bioavailability of nannozinone A was 8.82%. Plasma concentration of nannozinone A after the intravenous injection sharply decreased for 4 h but plasma concentration of orally administered nannozinone A showed fast distribution and slow elimination for 24 h. In conclusion, we successfully applied this newly developed sensitive LC-MS/MS analytical method of nannozinone A to the pharmacokinetic evaluation of this compound. This method can be useful for further studies on the pharmacokinetic opti-mization and evaluating the druggability of nannozinone A including its efficacy and toxicity.

Submission Date
2021-02-07
Revised Date
2021-03-16
Accepted Date
2021-03-25

Mass Spectrometry Letters