A highly sensitive HPLC–MS/MS method for quantification of 20( S )-protopanaxadiol in human plasma and its application in phase IIa clinical trial of a novel antidepressant agent

Jin, Ling; Yu, Yong; Zhu, Jiajun; Li, Yan; Li, Ling; Wang, Liping; Xu, Changjiang; Duan, Gengli

doi:10.1016/j.jchromb.2016.07.044

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…The amount of 20 S -PPD was determined by LC–MS/MS analysis as previously described [9] . The samples were injected into an Agilent LC–MS/MS system (Agilent Technologies, Santa Clara, CA, USA) equipped with an Agilent Technologies 1260 Infinity HPLC system and Agilent Technologies 6430 Triple Quad LC–MS system.…”

Section: Methodsmentioning

confidence: 99%

“…1 ) is a fully deglycosylated metabolite of ginsenosides Rb1, Rb2, Rb3, Rg3, Rh2, and compound K [8] . It has various pharmacological activities including antiestrogen, cardioprotective, antitumor, anti-inflammatory, and antidepressant effects [9] . Currently, a 20 S -PPD capsule is being developed as a novel antidepressant and is undergoing phase-IIa clinical trials in China [9] .…”

Section: Introductionmentioning

confidence: 99%

“…It has various pharmacological activities including antiestrogen, cardioprotective, antitumor, anti-inflammatory, and antidepressant effects [9] . Currently, a 20 S -PPD capsule is being developed as a novel antidepressant and is undergoing phase-IIa clinical trials in China [9] . Notably, a recent study demonstrated that 20 S -PPD showed markedly higher antiwrinkle and skin-whitening effects in immortalized human keratinocytes and 3D-cultured human skin equivalent models than compound K and Rb1 did, via the suppression of matrix metalloproteinases, which mediates the degradation of collagen and elastin in the skin [10] .…”

Section: Introductionmentioning

confidence: 99%

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Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies

Kim

Park

et al. 2018

Journal of Ginseng Research

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Background20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD.MethodsMEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model.ResultsA Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient r2 = 0.929‒0.947).ConclusionThe MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies

Kim

Park

et al. 2018

Journal of Ginseng Research

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“…The separation of PPD was carried out on an ACQUITY UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm, CA, USA) with the column temperature maintained at 35 °C. The mobile phase was composed of aqueous solution (A) and methanol (B) and was eluted at a flow rate of 0.20 mL/min following a gradient elution procedure, as shown in Table . − A Waters ACQUITY triple quadrupole (TQD) mass spectrometer (Waters Corp., Manchester, U.K.) was connected to the UPLC system via an electrospray ionization (ESI) interface, which was simultaneously operated both in positive and in negative ion mode. Quantification was performed using selective ion monitoring (SIM) of m / z [M + Na] + 483.37 for PPD and m / z [M + H] + 373.96 for finasteride. ,, …”

Section: Materials and Methodsmentioning

confidence: 99%

Human Serum Albumin Nanoparticles as a Carrier of 20(S)-Protopanaxadiol via Intramuscular Injection to Alleviate Cyclophosphamide-Induced Myelosuppression

Liu,

Yang,

Yuan

et al. 2023

Mol. Pharmaceutics

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“…20(S)-Protopanaxadiol (PPD), a fully deglycosylated active metabolite in the gastrointestinal tract derived from various ginsenosides such as Rb1, Rb2, Rb3, Rh2, Rg3, Rg2, and compound K, has drawn attention because of its diverse and valuable pharmacological activities [1][2][3]. PPD has been known to exert antitumor, antimetastasis, antiestrogen, anti-inflammatory, cardioprotective, antidepression, and anti-photoaging (i.e., antiwrinkle and skin-whitening) effects [4,5]. Its various therapeutic effects…”

Section: Introductionmentioning

confidence: 99%

Development of 20(S)-Protopanaxadiol-Loaded SNEDDS Preconcentrate Using Comprehensive Phase Diagram for the Enhanced Dissolution and Oral Bioavailability

Kim

Jang

et al. 2020

Pharmaceutics

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In this study, we aimed to develop a 20(S)-protopanaxadiol (PPD)-loaded self-nanoemulsifying drug delivery system (SNEDDS) preconcentrate (PSP) using comprehensive ternary phase diagrams for enhanced solubility, physical stability, dissolution, and bioavailability. Capmul MCM C8 and Capryol 90 were selected as the oil phase owing to the high solubility of PPD in these vehicles (>15%, w/w). Novel comprehensive ternary phase diagrams composed of selected oil, surfactant, and PPD were constructed, and the solubility of PPD and particle size of vehicle was indicated on them for the effective determination of PSP. PSPs were confirmed via particle size distribution, physical stability, and scanning electron microscope (SEM) with the dispersion of water. The optimized PSP (CAPRYOL90/Kolliphor EL/PPD = 54/36/10, weight%) obtained from the six possible comprehensive ternary phase diagrams showed a uniform nanoemulsion with the particle size of 125.07 ± 12.56 nm without any PPD precipitation. The PSP showed a dissolution rate of 94.69 ± 2.51% in 60 min at pH 1.2, whereas raw PPD showed negligible dissolution. In oral pharmacokinetic studies, the PSP group showed significantly higher C max and AUC inf values (by 1.94-and 1.81-fold, respectively) than the raw PPD group (p < 0.05). In conclusion, the PSP formulation with outstanding solubilization, dissolution, and in-vivo oral bioavailability could be suggested using effective and comprehensive ternary phase diagrams.Pharmaceutics 2020, 12, 362 2 of 15 are considered to be mediated via stimulation of the central nervous system, induction of apoptosis, and protection from DNA injury or chemoprophylaxis [6][7][8][9][10][11]. It has been reported that PPD possesses similar or stronger pharmacological activities than representative ginsenosides, Rh2 and Rg3 [12]. PPD, an active metabolite form itself, exerts various therapeutic benefits upon administration via oral or topical routes. However, PPD has extremely poor water solubility (<50 ng/mL), which limits its oral absorption [13]. Therefore, to enhance the oral bioavailability of PPD, its aqueous solubility should be improved by preparing oral formulations using an appropriate solubilization technology.To improve the dissolution and in-vivo oral bioavailability of PPD, researchers have utilized several formulation technologies, such as nanosuspension formulations prepared by anti-solvent precipitation methods or solid dispersions by melting solvent methods [12,14]. However, these methods had several disadvantages, including complicated preparation processes, low yield, and limited bioavailability. The structure of PPD comprises a tetracyclic terpene sapogenin containing hydrocarbon rings, which makes this molecule water-insoluble and fairly lipophilic (Figure 1). As a solubilization technology, the self-nanoemulsifying drug delivery system (SNEDDS) has been widely applied to enhance the aqueous solubility of highly lipophilic drugs such as PPD [15][16][17][18][19]. SNEDDS formulations are generally composed of oils, surfactant...

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A highly sensitive HPLC–MS/MS method for quantification of 20( S )-protopanaxadiol in human plasma and its application in phase IIa clinical trial of a novel antidepressant agent

Cited by 8 publications

References 17 publications

Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies

Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies

Human Serum Albumin Nanoparticles as a Carrier of 20(S)-Protopanaxadiol via Intramuscular Injection to Alleviate Cyclophosphamide-Induced Myelosuppression

Development of 20(S)-Protopanaxadiol-Loaded SNEDDS Preconcentrate Using Comprehensive Phase Diagram for the Enhanced Dissolution and Oral Bioavailability

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