The LC-MS/MS-Based Measurement of Isopimaric Acid in Rat Plasma and Application of Pharmacokinetics

  • Biomed Res Int. 2021 Oct 15:2021:2310422. doi: 10.1155/2021/2310422.
Doudou Huang  1  2 ,  Jiaxi Cheng  1  2 ,  Junqin Mao  3 ,  Senlin Ma  4 ,  Zenan Du  1  2 ,  Wansheng Chen  2  5 ,  Feng Zhang  5 ,  Lianna Sun  1
Affiliations
  • 1. Department of TCM Processing, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 2. Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 3. Department of Clinical Pharmacy, Shanghai Jiangqiao Hospital Jiading Branch, Shanghai 201803, China.
  • 4. Emergency Department, Huashan Hospital, Fudan University, Shanghai 200040, China.
  • 5. Department of Pharmacy, Changzheng Hospital, Navy Military Medical University, Shanghai 200433, China.
PMID: 34692827 DOI: 10.1155/2021/2310422
Abstract

Isopimaric acid (IPA) exhibits a diverse array of pharmacological activities, having been shown to function as an antihypertensive, antitumor, Antibacterial, and hypocholesterolemic agent. However, few studies of the pharmacokinetics of IPA have been performed to date, and such analyses are essential to explore the in vivo mechanisms governing the biological activity of this compound. As such, we herein designed a selective LC-MS approach capable of quantifying serum IPA levels in model rats using an Agilent HC-C18 column (250 mm × 4.6 mm, 5 μm) via isocratic elution with a mobile phase composed of methanol 0.5% formic acid (91 : 9, v/v) at a 1 mL/min flow rate. Ion monitoring at m/z 301.2 [M-H]- was used to quantify IPA levels in plasma samples from these rats, while internal standard (IS) levels were assessed at m/z 455.3 [M-H]-. After validation, this approach was employed to conduct a pharmacokinetic analysis of rats administered IPA via the oral (p.o. 50, 100, or 200 mg/kg) and intravenous (i.v. 5 mg/kg) routes. Analyses of noncompartmental pharmacokinetic parameters revealed that IPA underwent secondary absorption following oral administration to these Animals, with the two tested oral doses (50 and 100 mg/kg) being associated with respective absolute bioavailability values of 11.9% and 17.5%. In summary, this study may provide a foundation for future efforts to explore the mechanistic basis for the pharmacological activity of IPA, offering insights to guide its subsequent clinical utilization.

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