Development and validation of an UPLC‐Q/TOF‐MS assay for the quantitation of neopanaxadiol in beagle dog plasma: Application to a pharmacokinetic study

Abstract

Neopanaxadiol (NPD), the main panaxadiol constituent of Panax ginseng C. A. Meyer (Araliaceae), has been regarded as the active component for the treatment of Alzheimer's disease. However, few references are available about pharmacokinetic evaluation for NPD. Accordingly, a rapid and sensitive method for quantitative analysis of NPD in beagle dog plasma based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry was developed and validated. Analytes were extracted from plasma by liquid-liquid extraction and chromatographic separation was achieved on an Agilent Zorbax Stable Bond C column. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions both at m/z 461.4 → 425.4 for NPD and internal standard of panaxadiol. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, were within acceptable ranges and the method was appropriate for multitude sample determination. After oral intake, NPD was slowly absorbed and eliminated from circulatory blood system and corresponding plasma exposure was low. Application of this quantitative method will yield the first pharmacokinetic profile after oral administration of NPD to beagle dog. The information obtained here will be useful to understand the pharmacological effects of NPD.

The antitumor activity and pharmacokinetics research of PPD‐Arg (Tos) using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry

“…Although the pharmacokinetic profiles of PPD and PAT were significantly different, obvious double peaks were observed in the concentration–time profiles of both groups, which were consistent with the results of previous pharmacokinetic studies on panaxadiol (Geng et al, 2017). The peak pattern for PPD was consistent with that reported in the literature.…”

“…The T max values of both were less, showing that PPD ginsenosides were mainly absorbed directly into the plasma. Previous study has shown that PPD was rapidly eliminated from the body, with a t 1/2 of 2 h, and the oral bioavailability in rats was about 30% (Bao et al, 2013) Although the pharmacokinetic profiles of PPD and PAT were significantly different, obvious double peaks were observed in the concentration-time profiles of both groups, which were consistent with the results of previous pharmacokinetic studies on panaxadiol (Geng et al, 2017). The peak pattern for PPD was consistent with that reported in the literature.…”

“…However, previous reports have shown that the PPD-type ginsenosides were affected by low plasma exposure and bioavailability (Geng et al, 2017). 20(s)-PPD has low polarity and poor water solubility, which is relatively difficult to be absorbed orally (Kim et al, 2020).…”

Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis

“…Ginsenosides can be converted into hydrophobic compounds by the intestinal microbial enzymes, and are then transported to the liver, which metabolizes these hydrophobic metabolites into hydrophilic compounds through phase I–III enzymes. Information from the literature concerning the PK studies of ginseng is given in Table S8 † 336,342,346–370 . These studies involve a systematic description of the absorption, distribution, metabolism, excretion, and blood concentration of ginsenosides over time after administering pure compounds (involving Rh4/Rk3, 346 25-OCH 3 -PPD/25-OH-PPD, 347 neopanaxadiol, 348 26-OH-PPD, 349 PPD, 350 24-OH-PPD, 351 Rb3, 352 Rc, 353 noto-Fc, 355 CK, 336 Rb1, 356 octillol/RT5/F11, 357 and Rd 358 ) or ginseng extracts (white ginseng, 342 fermented and nonfermented P. ginseng , 359 red ginseng, 362 P. quinquefolius , 365 and P. notoginseng 366) to healthy humans or animals.…”

LC‐MS based metabolic and metabonomic studies of Panax ginseng

“…Notably, ginseng berry extract showed a superior oral absorption of ginsenoside Re ( F % 0.33–0.75) at equivalent ginsenoside Re dose to pure ginsenoside Re, indicating that ginseng berry extract might be a good form for ginsenoside Re intake . A rapid and sensitive method is developed and validated for quantitative analysis of neopanaxadiol in beagle dog plasma based on ultra‐performance liquid chromatography quadruple time of flight mass spectrometry (UPLC‐Q‐TOF‐MS) …”