Gas chromatographic–mass spectrometric analysis of d-limonene in human plasma

Wang, Shurong; Chen, Yu; Gao, Zhaoxia; Xiong, Meijin; Zhong, Zhaohui; Ye, Liming

doi:10.1016/j.jpba.2007.04.018

Cited by 17 publications

(11 citation statements)

References 17 publications

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“…Plasma d -limonene concentrations were determined using a published assay (19) with minor modifications. Briefly, plasma samples or plasma calibration standards (100 μ l) were mixed with an equal volume of the internal standard solution (1.2 mg/l of perillyl aldehyde in 100% acetonitrile) to precipitate the plasma proteins.…”

Section: Methodsmentioning

confidence: 99%

Adipose Tissue Accumulation ofd-Limonene With the Consumption of a Lemonade Preparation Rich ind-Limonene Content

Miller

Hakim

Chew

et al. 2010

Nutrition and Cancer

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d-Limonene is a bioactive food component found in high concentration in citrus peel oil with anticancer effects in preclinical studies of mammary carcinogenesis. Extrapolation of preclinical data to human cancer is limited, in part, by inadequate information on the oral bioavailability and tissue disposition of d-limonene in humans. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast. To assess disposition of d-limonene in humans, we conducted a pilot study of oral d-limonene-rich lemonade. Following a 1-wk washout period devoid of citrus, healthy adults consumed 40 oz. of freshly prepared lemonade containing 500 to 600 mg d-limonene daily for 4 wk. On the first and last consumption days, blood and buttock fat biopsy were collected. Matched preintervention and postintervention fat biopsies (n = 7), and matched preintervention and postintervention plasma samples (n = 6), were analyzed for d-limonene levels using gas chromatography and mass spectrometry. There was a significant increase in d-limonene levels in the fat biopsies after 4 wk (P = 0.009); initial levels ranged from nondetectable to 7.79 μmol/kg tissue, and postintervention levels ranged from 53.6 to 294 μmol/kg tissue. Plasma d-limonene levels increased from 0.35 to 0.72 μmol/l initially to postintervention levels of 0.54 to 1.65 μmol/l (P = 0.016). Postintervention adipose d-limonene levels were 51.0 to 195 times higher than plasma levels (P = 0.009). Our results demonstrate accumulation of d-limonene in adipose tissue after oral dosing and support additional studies of d-limonene for chemoprevention in tissues such as the breast that are comprised of a significant fat fraction.

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Section: Methodsmentioning

confidence: 99%

Adipose Tissue Accumulation ofd-Limonene With the Consumption of a Lemonade Preparation Rich ind-Limonene Content

Miller

Hakim

Chew

et al. 2010

Nutrition and Cancer

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show abstract

“…Limonene concentrations in plasma and NAF were determined using a published assay [11] with minor modifications. Briefly, plasma or NAF samples (50 µL) were mixed with an equal volume of the internal standard solution (1.2 µg/mL of perillyl aldehyde in 100% acetonitrile) and then extracted with hexane.…”

Section: Methodsmentioning

confidence: 99%

Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast

Miller¹,

Thompson²,

Hakim³

et al. 2012

JCT

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Background Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. Materials and Methods We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. Results The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. Conclusions Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.

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“…Limonene is the principal constituent of citrus oils [34]. It is used in the production of foods and cleaning products to provide lemon and orange fragrances [35].…”

Section: Important Compoundsmentioning

confidence: 99%

Analytical pyrolysis of tobacco residue: Effect of temperature and inorganic additives

Cardoso

Ataíde

2013

Journal of Analytical and Applied Pyrolysis

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Gas chromatographic–mass spectrometric analysis of d-limonene in human plasma

Cited by 17 publications

References 17 publications

Adipose Tissue Accumulation ofd-Limonene With the Consumption of a Lemonade Preparation Rich ind-Limonene Content

Adipose Tissue Accumulation ofd-Limonene With the Consumption of a Lemonade Preparation Rich ind-Limonene Content

Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast

Analytical pyrolysis of tobacco residue: Effect of temperature and inorganic additives

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