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.
Highlights
Rosin acids including isopimaric acid (IPA), sandaracopimaric acid, and pimaric acid are major bioactive derivatives of Pinus genus member plants
After a 7-day acclimatization period, 20 rats were randomly assigned to undergo the administration of IPA via p.o. administration (50, 100, or 200 mg/kg) or via i.v. injection (5 mg/kg) for pharmacokinetic analyses
ESI parameters were optimized via flow injection analysis (FIA) using the IPA standards, with the following time segments being recorded: 8– 11 min for internal standard (IS) m/z 455.3 and 11–14 min IPA at m/z 301.2
Summary
Rosin acids including isopimaric acid (IPA), sandaracopimaric acid, and pimaric acid are major bioactive derivatives of Pinus genus member plants. IPA is a diterpenoid containing a double bond and methyl and ethenyl residues at C-12 that has previously been reported to exhibit antibacterial [5], antitumor [6, 7], and hypocholesterolemic activity [8], in addition to being able to prevent high blood pressure via the activation of a large conductance Ca2+ and K+ channel [9, 10] Preparations containing this compound, including Kanglao, Cebai NO.V, and IPA capsules, are often used to treat pulmonary tuberculosis patients in Chinese clinics, wherein they have been found to exhibit marked efficacy against this disease. Precision, sensitivity, and specificity of this approach, we applied it to study the pharmacokinetics of IPA following its oral and i.v. administration in rats
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