Gas chromatographic–mass spectrometric analysis of perillyl alcohol and metabolites in plasma

Chen, Haitao; Chan, Kenneth K.; Budd, Thomas; Ganapathi, Ram

doi:10.1016/s0378-4347(99)00065-1

Cited by 31 publications

(15 citation statements)

References 11 publications

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“…Such investigations have shown that there are compounds found in trace amounts in lavender oils which have potentially significant anticancer activity [49]. One such component, the monoterpenoid perillyl alcohol, has been investigated as a potential component of anticancer treatments [50], and has been shown to inhibit angiogenic cell growth and division in vitro [51]. Subsequent studies into the chemoprevention potential of perillyl alcohol were undertaken in National Cancer Institute-sponsored phase I, II, and III trials for prostate, breast, and colon cancers.…”

Section: Studies In Model Speciesmentioning

confidence: 99%

Biosynthesis and Therapeutic Properties ofLavandulaEssential Oil Constituents

Woronuk

Demissie²,

Rheault³

et al. 2010

Planta Med

179

122

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Section: Studies In Model Speciesmentioning

confidence: 99%

Biosynthesis and Therapeutic Properties ofLavandulaEssential Oil Constituents

Woronuk

Demissie²,

Rheault³

et al. 2010

Planta Med

179

122

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“…After ingestion, LMN is completely absorbed and undergoes extensive metabolism in humans (Kodama et al 1976;Vigushin et al 1998). methyl-3-cyclohexene-1-yl)-1,2-propanediol, , limonene-1,2-diol [1-methyl-4-(1-methylethenyl) cyclohexane-1,2-diol, LMN-1,2-OH] (Kodama et al 1976;Poon et al 1996), and perillic acid [(1-methylethenyl)-1-cyclohexene-1-carboxylic acid, PA] (Crowell et al 1994) which may originate from the intermediate product perillyl alcohol [(4-(1-methylethenyl)-1-cyclohexene-1-methanol; POH] (Zhang et al 1999) were found to be prominent LMN metabolites. Another previously identified metabolite is dihydroperillic acid [4-(1-methylethenyl)-cyclohexanecarboxylic acid, DHPA] (Crowell et al 1994).…”

Section: Introductionmentioning

confidence: 99%

R-Limonene metabolism in humans and metabolite kinetics after oral administration

Schmidt

Göen

2016

Arch Toxicol

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We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100-130 µg kg bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected. From two subjects, blood samples were drawn up to 5 h after exposure. The parent compound was analysed in blood using headspace GC-MS. The metabolites cis- and trans-carveol (cCAR), perillyl alcohol (POH), perillic acid (PA), limonene-1,2-diol (LMN-1,2-OH), and limonene-8,9-diol (LMN-8,9-OH) were quantified in both blood and urine using GC-PCI-MS/MS. Moreover, GC-PCI-MS full-scan experiments were applied for identification of unknown metabolites in urine. In both matrices, metabolites reached maximum concentrations 1-2 h post-exposure followed by rapid elimination with half-lives of 0.7-2.5 h. In relation to the other metabolites, LMN-1,2-OH was eliminated slowest. Nonetheless, overall renal metabolite elimination was completed within the 24-h observation period. The metabolite amounts excreted via urine corresponded to 0.2 % (cCAR), 0.2 % (tCAR), <0.1 % (POH), 2.0 % (PA), 4.3 % (LMN-1,2-OH), and 32 % (LMN-8,9-OH) of the orally administered dose. GC-PCI-MS full-scan analyses revealed dihydroperillic acid (DHPA) as an additional LMN metabolite. DHPA was estimated to account for 5 % of the orally administered dose. The study revealed that human LMN metabolism proceeds fast and is characterised by oxidation mainly of the exo-cyclic double bond but also of the endo-cyclic double bond and of the methyl side chain. The study results may support the prediction of the metabolism of other terpenes or comparable chemical structures.

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“…The significance of the slope coefficients of the estimated lines was verified by analysis of variance (ANOVA) and F-test (critical F-value = 4,381, considering 1 numerator degree of freedom and n − 2 denominator degrees of freedom, with a 5% significance level). The values of F for the curves were: curve 1: F (1,19) = 55577.6, p < 0.05; curve 2: F (1,19) = 29997.5, p < 0.05; curve 3: F (1,19) = 48517.1, p < 0.05. All values of F were larger than the critical F-value, indicating that the proposed models are suitable for describing the phenomenon.…”

Section: Resultsmentioning

confidence: 99%

“…The most common technique used is the gas chromatography coupled to mass spectrometry (GC-MS) for both biological matrices such as plasma and urine, and non-biological matrices such as the volatile fraction of plant extracts. [19][20][21][22][23][24] Methods by liquid chromatography (LC) techniques are also described in the literature, such as liquid chromatography-diode array detection (LC-DAD), [25][26][27][28][29] liquid chromatographyelectrochemical detection (LC-ECD) 30 and liquid chromatography-fluorescence detection (LC-FLD). 31 These papers are devoted to describing chromatographic methods for analytical and bioanalytical quantification of POH, and none of these cases comprise a degradation behavior study.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Stability-Indicating Method for Perillyl Alcohol Incorporated in Poly(lactide-co-glycolide) Nanoparticles and Stress Degradation Studies

Marson

Vilhena

Pontes

et al. 2017

J. Braz. Chem. Soc.

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Perillyl alcohol has been studied in the treatment of cancer disease. However, its high toxicity is a drawback, which can be overcome by its incorporation in nanostructured systems. The aim of this work was to develop and validate a chromatographic method for determination of perillyl alcohol encapsulation efficiency in a polymeric nanoparticles formulation and evaluation of the presence of related degradation products. Perillyl alcohol was subjected to forced conditions of hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as suggested in the International Conference of Harmonization (ICH) guidelines. The drug showed significant degradation under acidic conditions. The degradation products could be adequately separated on an XBridge C18 column (100 × 2.1 mm, 3.5 μm) using isocratic elution (350 μL min , precise (relative standard deviation (RSD) < 2.0%), accurate (98.07 to 101.99%) and robust for minor changes. The method was successfully applied to determine the encapsulation efficiency of perillyl alcohol in polymeric nanoparticles, both for product development and for quality control purposes. After nanoparticles production, the presence of degradation products was not observed indicating that the single-emulsion solvent-evaporation technique used does not favor chemical degradation of the drug.

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Gas chromatographic–mass spectrometric analysis of perillyl alcohol and metabolites in plasma

Cited by 31 publications

References 11 publications

Biosynthesis and Therapeutic Properties ofLavandulaEssential Oil Constituents

Biosynthesis and Therapeutic Properties ofLavandulaEssential Oil Constituents

R-Limonene metabolism in humans and metabolite kinetics after oral administration

Development and Validation of a Stability-Indicating Method for Perillyl Alcohol Incorporated in Poly(lactide-co-glycolide) Nanoparticles and Stress Degradation Studies

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