Pharmacokinetic and tissue distribution studies of cassane diterpenoids, in rats through an ultra‐high‐performance liquid chromatography–Q exactive hybrid quadrupole–Orbitrap high‐resolution accurate mass spectrometry

Abstract

Cassane diterpenoids (CA) are considered as the main active constituents of medicinal plants belonging to the Caesalpinia genus. Three cassane derivatives, bonducellpin G (BG), 7-O-acetyl-bonducellpin C (7-O-AC) and caesalmin E (CE), isolated from Caesalpinia minax Hance seeds, showed strong anti-inflammatory activity. In this paper, pharmacokinetics (BG, 7-O-AC, CE) and tissue distribution (7-O-AC, CE) properties were studied for the first time using a reliable, sensitive and rapid UHPLC-Q-Orbitrap HR-MS to develop new anti-inflammatory agents. A novel quantitative method with full scan in positive ion mode was used to determine the contents of compounds. They were separated using acetonitrile-water (0.1% formic acid) as gradient mobile phase. The calibration curve displayed good linearity and the lower limit of quantitation was 0.005-0.02 μg/mL for all analytes. Meanwhile, the absorption, distribution, metabolism, excretion (ADME) property was predicted using PreADMET web. The pharmacokinetic parameters indicated that they were absorbed quickly, eliminated rapidly together with high blood concentration. The results of tissue distribution demonstrated that CE was distributed rapidly and widely among tissues, and stomach was the main tissue site of CE and 7-O-AC, followed by small intestine/liver. This study indicates that the structures and dosages of active CA should be modified to help improve the absorption rate and residence time, and the findings are helpful for the pharmaceutical design of CA derivatives.Abbreviations: CA, cassane diterpenoids; FS, full scan; UHPLC-Q-Orbitrap-HR-MS, ultra-high-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry.

Comparative Study on Pharmacokinetics of Four Active Compounds in Rat Plasma after Oral Administration of Raw and Wine Processed Chuanxiong Rhizoma

“…Q Exactive Focus Orbitrap mass system equipped with high selective performance of quadrupole and high resolving power of Orbitrap has advantages of superior accuracy (10 −7 -10 −6 ), high resolution (up to 1,000,000) and excellent sensitivity [25]. It can provide multiple scan patterns, like full scan, parallel reaction monitoring, and selected ion monitoring.…”

Discovery of diversified cassane diterpenoids as potent antibacterial agents from Caesaplinia pulcherrima and their mechanisms

“…In summary, 21 terpenoids, including 11 diversified cassane diterpenoids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), and 10 known sesquiterpenes, were isolated and identified from stems of C. pulcherrima. Notably, compounds 1-6 featured an aromatic C ring, representing a rare class of cassane diterpenes which attract particular attention due to their significant biological activities.…”

“…As shown in Table 7, compounds 1, 3, and 6, possessing an aromatic C ring, exhibited more potent antifeedant activity against P. xylostella than the cassane diterpenoids (7)(8)(9). Additionally, compounds 6 showed more significant antifeedant activity against P. xylostella than against M. separate (EC 50 11.98 vs 29.11 μg cm −2 ), while the antifeedant activity of compound 3 against P. xylostella and M. separate was comparable according to their EC 50 values of 25.61 and 25.32 μg cm −2 .…”

“…Cassane diterpenes, with a molecular skeleton constructed from the fusion of three cyclohexane rings and a furan ring or butanolide lactone, are the main and characteristic secondary metabolites of traditional medicinal plants belonging to the genus Caeselpinia. 8,9 Modern pharmacological studies indicate that cassane diterpenoids perform many functions, including antiinflammatory, antitumor, antimalarial, antimicrobial, antiviral, antioxidant, and antinociceptive properties. 10,11 They can potentially be botanical bactericides and serve as lead candidates for the design and synthesis of new diterpenoid bactericides for agricultural applications.…”

What is the role of current mass spectrometry in pharmaceutical analysis?

“…A hybrid QqQ linear ion‐trap is a less employed mass analyzer (Tanner et al, 2019). To date, LC‐HRMS is starting to be used for the pharmacokinetic studies of small molecules, for example, LC coupled with quadrupole in tandem with Orbitrap (Alkhateeb et al, 2020; Park et al, 2021; Qian et al, 2022; Wang, Wang, et al, 2019). The number of publications on this topic has been rising every year.…”