PMID- 37148697 OWN - NLM STAT- MEDLINE DCOM- 20230612 LR - 20230612 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 233 DP - 2023 Sep 5 TI - Pharmacokinetic and tissue distribution study of six saponins in the rat after oral administration of Ilex pubescens extract using a validated simultaneous UPLC-qTOF-MS/MS assay. PG - 115431 LID - S0731-7085(23)00200-5 [pii] LID - 10.1016/j.jpba.2023.115431 [doi] AB - Ilex pubescens Hook. et Arn is a medicinal plant of the Ilex family that is mainly used for the treatment of cardiovascular diseases. Its main medicinal ingredients are total triterpenoid saponins (IPTS). However, the pharmacokinetics and tissue distribution of the main multi-triterpenoid saponins are lacking. This is the first report that demonstrates a sensitive ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF-MS/MS) method for the quantification of ilexgenin A (C1), ilexsaponin A1 (C2), ilexsaponin B1 (C3), ilexsaponin B2 (C4), ilexsaponin B3 (DC1) and ilexoside O (DC2) in rat plasma and various tissues of the heart, liver, spleen, lungs, kidney, brain, stomach, duodenum, jejunum, ileum, colon and thoracic aorta. The chromatographic separation was carried out on an Acquity HSS T3 UPLC column (2.1 x 100 mm, 1.8 microm, Waters, USA) with a mobile phase consisting of 0.1% (v/v) formic acid (A) and acetonitrile containing 0.1% (v/v) formic acid (B) at a flow rate of 0.25 mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using selected ion monitoring (SIM) in negative scan mode. The developed quantification method showed good linearity over the concentration range of 10-2000 ng/mL for plasma and 25-5000 ng/mL for tissue homogenates with R(2) >/= 0.990. Lower limits of quantification (LLOQ) was 10 ng/mL in plasma and 25 ng/mL in tissue homogenates. The intra- and inter-day precision were less than 10.39%, and the accuracy was between - 1.03% and 9.13%. The extract recoveries, dilution integrity and matrix effect were well within satisfactory limits. Using the validated method, the pharmacokinetic parameters, including half-life, AUC, Cmax, CL, and MRT, of six triterpenoid saponins in rats after oral administration were provided by establishing their plasma concentration-time curves, while their absolute quantification in various tissues after oral administration was also determined at first, which provides a scientific basis for their clinical application. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Chen, Bingying AU - Chen B AD - School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. FAU - Kuang, Guojun AU - Kuang G AD - Division of Biochemistry Drug's, Guangzhou Institute for Drug Control, Guangzhou 510160, China. FAU - Wang, Ying AU - Wang Y AD - School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. FAU - Zhang, Yingyin AU - Zhang Y AD - School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. FAU - Wu, Yurong AU - Wu Y AD - School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. FAU - Li, Yu AU - Li Y AD - School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. FAU - Zhang, Juan AU - Zhang J AD - Division of Biochemistry Drug's, Guangzhou Institute for Drug Control, Guangzhou 510160, China. FAU - Zhang, Lei AU - Zhang L AD - School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: zhangleic431@163.com. LA - eng PT - Journal Article DEP - 20230428 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - 0YIW783RG1 (formic acid) RN - 0 (Saponins) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Triterpenes) SB - IM MH - Rats MH - Animals MH - Tandem Mass Spectrometry/methods MH - Chromatography, High Pressure Liquid/methods MH - Tissue Distribution MH - *Ilex/chemistry MH - *Saponins/chemistry MH - *Drugs, Chinese Herbal/chemistry MH - Administration, Oral MH - *Triterpenes/chemistry OTO - NOTNLM OT - Ilex pubescens Hook. et Arn OT - Pharmacokinetics OT - Tissue distribution OT - Triterpenoid saponin OT - UPLC-qTOF-MS/MS COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/05/07 00:42 MHDA- 2023/06/12 06:42 CRDT- 2023/05/06 18:06 PHST- 2023/03/07 00:00 [received] PHST- 2023/04/25 00:00 [revised] PHST- 2023/04/27 00:00 [accepted] PHST- 2023/06/12 06:42 [medline] PHST- 2023/05/07 00:42 [pubmed] PHST- 2023/05/06 18:06 [entrez] AID - S0731-7085(23)00200-5 [pii] AID - 10.1016/j.jpba.2023.115431 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2023 Sep 5;233:115431. doi: 10.1016/j.jpba.2023.115431. Epub 2023 Apr 28.