Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

Abstract

Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography−tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/ mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration's bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy.

Redox-Responsive Hyaluronic Acid–Tacrolimus Conjugate: Synthesis, Characterization, and In Vitro Immunosuppressive Activity

“…The whole blood stability of the HA-ss-TAC conjugate was assessed in rat blood using a previously reported protocol. , Fresh whole blood was obtained from control Wistar rats in our institutional animal house. A stock solution of HA-ss-TAC conjugate was prepared in a solvent mixture of DMSO and water: (20:80, % v/v).…”

“…The metabolic stability study of TAC and its conjugate was performed in human liver microsomes (HLM) using our earlier reported protocol . The stock solutions of TAC or its conjugate were prepared in DMSO or 20% DMSO + 80% water (v/v), respectively, and diluted further with acetonitrile.…”

“…The metabolic stability study of TAC and its conjugate was performed in human liver microsomes (HLM) using our earlier reported protocol. 57 The stock solutions of TAC or its conjugate were prepared in DMSO or 20% DMSO + 80% water (v/v), respectively, and diluted further with acetonitrile. Briefly, phosphate buffer (0.1 M, pH 7.4) containing magnesium chloride (3.3 mM) and microsomal protein (HLM, 0.5 mg/mL) was preincubated (5 min) in a pre-heated shaking water bath at 37 °C.…”

Multitargeted C9‐substituted ester and ether derivatives of berberrubine for Alzheimer's disease: Design, synthesis, biological evaluation, metabolic stability, and pharmacokinetics

“…The metabolic stability study of 12a and 13 was performed in HLM and RLM using our earlier reported protocol (Dogra, Kotwal, et al, 2020; Manhas et al, 2021; M. Sharma et al, 2022). The incubation of test compounds with microsomal proteins was done with and without the presence of NADPH at 0, 15, and 30 min time points.…”

“…The metabolic stability study of 12a and 13 was performed in HLM and RLM using our earlier reported protocol Manhas et al, 2021;M. Sharma et al, 2022).…”