Determination and Pharmacokinetic Study of Pachymic Acid by LC-MS/MS

Abstract

Poria cocos is a well-known medicinal plant widely used in China and other East Asian countries owing to its various therapeutic effects. Pachymic acid (PA) is a bioactive lanostrane-type triterpenoid from Poria cocos. In this paper, a method of high-performance liquid chromatographic (LC) coupled with triple quadrupole tandem mass spectrometry (QQQ-MS/MS) was developed and validated to investigate the concentration of PA in rat plasma. Samples were prepared by a liquid-liquid extraction, and chromatographic separation was achieved with a Phenomenex Gemini C 18 column (50 mm 2.0 mm i.d.) using a mobile phase consisting of acetonitrile and 0.05% formic acid (85 : 15, v/v) at a flow rate of 0.3 mL/min. The detection was performed on an Applied Bio-Systems API 4000 MS/MS with an electrospray ionization (ESI) inlet in negative multiple reaction monitoring (MRM) mode. Standard curves of samples in plasma were linear (R 2 0.9948) over the concentration range of 5-500 ng/mL, and acceptable accuracy and precision were achieved. The lower limit of quantification and detection were 5 and 0.5 ng/mL, respectively. The method was used successfully to study the pharmacokinetics of PA in rats for oral administration. The main pharmacokinetic parameters of elimination half-life (t 1/2 ), area under the plasma concentration-time curve from time zero to infinity (AUC 0→∞ ), plasma clearance (CL), and apparent volume of distribution (V d ) for the PA group were 4.96 1.33 h, 1466.9 361.7 ng·h/mL, 6.82 1.73 L/h, and 48.85 9.47 L, respectively. This LC-MS/MS method can be developed further for clinical investigation of PA-containing products. Key words Poria cocos; pachymic acid; quantitation; rat plasma; pharmacokinetics; LC-MS/MSBecause of their low toxicities and high levels of effectiveness against many diseases, traditional Chinese medicines (TCMs) have played an important role in the health of the Chinese people for thousands of years. In addition, they have gained ever-increasing global attention owing to the desirability of their bioactive compounds for the discovery of novel drug candidates. Poria cocos, which is also known as Fu Ling, is often used in TCM for its diuretic and sedative effects. 1) P. cocos alone or in combination with other herbs is often used to treat diabetes as well as other disorders. 2-4)The main ingredients of this herbal medicine include a group of triterpenoid compounds. Pachymic acid (PA) is one of the major components in P. cocos and plays an important role in various pharmacological effects. For example, PA has shown anti-inflammatory, 5)anti-apoptotic, and anti-immunologic rejection effects.6) In addition, it has exhibited cytotoxicity against a human colon carcinoma cell line.1,7) Furthermore, PA has been shown to induce apoptosis of human prostate cancer cells by reducing prostaglandin synthesis and AKT activity, 8,9) to stimulate glucose uptake, 10) and to inhibit the phospholipase A2 family of arachidonic acid-producing enzymes.11) Therefore, further pharmacodynamic and pharmacokinetic studie...

Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms

“…In addition, a study performed by Wang et al reported main pharmacokinetic parameters of pachymic acid, a bioactive triterpenoid isolated from Poria cocos, after oral intake. The half-life was 4.96 ± 1.33 h and t max was 0.75 ± 0.14 h [92].…”

Pharmacological profiles and therapeutic applications of pachymic acid (Review)

“…After sublingual vein injection of PA at a dose of 30 mg/kg, the pharmacokinetic parameters in rat plasma were obtained using HPLC with half-life (t 1 / 2 ) at 8.79±6.80 h, clearance (CL) at 0.53±0.28 l/h, area under the curve (AUC) 0-∞ at 18.90±9.39 µ g h/ml and mean residence time 0-∞ at 12.58±9.95 h ( 89 ). Following oral administration of PA (10 mg/kg), the main pharmacokinetic parameters in rat plasma using liquid chromatography tandem mass spectrometry (MS) were elimination half-life at 4.96±1.33 h, AUC 0-∞ at 1466.9±361.7 ng h/ml and CL at 6.82±1.73 l/h ( 90 ). Determination of PA (12.3 mg/kg) in rats after oral administration using UPLC-Q-Orbi-trap MS demonstrated that the pharmacokinetic parameters were terminal half-life at 11.51±9.90 h, AUC 0-∞ at 336.29±161.99 ng h/ml and CL at 45.07±73.64 L/h.…”

Poria Cocos Ameliorates Bone Loss in Ovariectomized Mice and Inhibits Osteoclastogenesis In Vitro

“…Therefore, the beneficial effects of PC on estrogen-deprivation-induced bone loss may be due to the activity of the constituents mentioned above. In addition, numerous pharmacokinetic studies have reported that dehydrotumulosic acid, poricoic acid A, polyporenic acid C, dehydropachymic acid, pachymic acid, and dehydrotrametenolic acid are absorbed, distributed, metabolized, and excreted after oral administration of PC [9,26,30]. Further studies are needed to elucidate the precise mechanisms of components responsible for the anti-osteoporotic activity shown by PC and its effects on bone homeostasis.…”