Quantification of Endogenous Retinoic Acid in Human Plasma by Liquid Chromatography/Mass Spectrometry

Huselton, Christine; Fayer, B.E.; Garland, William A.; Liberato, Daniel J.

doi:10.1021/bk-1990-0420.ch010

Cited by 9 publications

(1 citation statement)

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“…The right bronchus was ligated, and the right lung lobes were removed and frozen for later ATRA analysis. For plasma and lung tissue, as well as for filter samples collected during aerosolization experiments, ATRA concentrations were measured by a liquid chromatography-triple quadrupole mass spectrometry (LC/MS 3 ) technique using methods based on previous work [10,15]. Briefly, serial dilutions of ATRA standards in methanol were spiked into each sample matrix (lung, plasma, or filters) such that calibration accounted for recovery of material during extraction.…”

Section: Necropsy Tissue Analysis and Atra Measurementsmentioning

confidence: 99%

INHALATION ADMINISTRATION OF ALL-TRANS-RETINOIC ACID FOR TREATMENT OF ELASTASE-INDUCED PULMONARY EMPHYSEMA IN FISCHER 344 RATS

March

Cossey

Esparza

et al. 2004

Experimental Lung Research

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A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus, while inhalation treatment caused greater levels of the drug in lung tissue in comparison to that of injection-treated animals, treatment with ATRA by either route of administration did not cause a reversal of lung tissue damage in this model of elastase-induced emphysema.

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Section: Necropsy Tissue Analysis and Atra Measurementsmentioning

confidence: 99%

INHALATION ADMINISTRATION OF ALL-TRANS-RETINOIC ACID FOR TREATMENT OF ELASTASE-INDUCED PULMONARY EMPHYSEMA IN FISCHER 344 RATS

March

Cossey

Esparza

et al. 2004

Experimental Lung Research

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Percutaneous absorption of [3H]tretinoin and systemic exposure to mequinol after dermal application of 2% mequinol/0.01% [3H]tretinoin (Solagé®) solution in healthy volunteers

Everett

Franz

Chando

et al. 1999

Biopharm. Drug Dispos.

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Solagé® is a combination product composed of 2% mequinol (4‐hydroxyanisole) and 0.01% tretinoin (all‐trans‐retinoic acid) in an ethanolic solution, which is being studied for its safety and efficacy as a topical treatment for disorders of skin hyperpigmentation. The purpose of this study was to evaluate the extent of percutaneous absorption of [3H]tretinoin and to estimate the systemic exposure to mequinol from this combination product when topically applied to the backs of healthy subjects. Eight subjects received bid topical applications of nonradiolabelled 2% mequinol/0.01% tretinoin solution on a 400 cm2 area of the back for 14 days. The subjects then received a single topical application of 2% mequinol/0.01% [3H]tretinoin solution. After 12 h, the radiolabelled dose was removed and bid treatment with nonradiolabelled 2% mequinol/0.01% tretinoin solution was continued for 7 days. Plasma, urine and faecal samples were analysed for total radioactivity and plasma was analysed for both mequinol and tretinoin by GC/MS procedure. Mean percutaneous absorption of [3H]tretinoin based on the cumulative recoveries of radioactivity in the urine and faeces was about 4.5% (median 2.18%). Tretinoin concentrations in plasma did not increase above endogenous levels. This was consistent with the concentrations of radioactivity in plasma, which showed an average Cmax of 91 pg‐eq/mL (median 26 ng/mL). Average Cmax and AUC0–12 h values for mequinol were 10 ng/mL and 33 ng h/mL, respectively. Based on the results of this study, systemic toxicity from topical application of tretinoin in this formulation is unlikely, because percutaneous absorption of tretinoin is minimal and because endogenous levels of tretinoin are not increased following bid dosing with this combination formulation. The safety of mequinol in this combination formulation is supported by the low systemic exposures of the subjects in this study compared with the systemic exposures at the highest doses in the dermal toxicity studies in mice (16.6‐fold) and rats (34.6‐fold). Copyright © 1999 John Wiley & Sons, Ltd.

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Separation characteristics of molecular imprinted poly(methacrylic acid) for retinoid derivatives

Nam

Kim

2003

J of Applied Polymer Sci

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Methacrylic acid monomer was crosslinked in the presence of a template of either all-trans-retinoic acid or all-trans-retinol to prepare molecular imprinted polymers. The prepared molecular imprinted polymers showed good performance in the high-performance liquid chromatography (HPLC) separation of objective molecules from retinoid derivatives. The retention time increased with an increasing ratio of monomer to template, as more binding sites were statistically generated between host molecules and the template. The column capacity factor and selectivity were de-termined from the HPLC data. Not only specific interactions such as hydrogen bonding but also a tailor-made spatial cavity were the main functions of the separation of objective molecules. Thermal stability and prepared polymer particle shape were also investigated.

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Quantification of Endogenous Retinoic Acid in Human Plasma by Liquid Chromatography/Mass Spectrometry

Cited by 9 publications

References 0 publications

INHALATION ADMINISTRATION OF ALL-TRANS-RETINOIC ACID FOR TREATMENT OF ELASTASE-INDUCED PULMONARY EMPHYSEMA IN FISCHER 344 RATS

INHALATION ADMINISTRATION OF ALL-TRANS-RETINOIC ACID FOR TREATMENT OF ELASTASE-INDUCED PULMONARY EMPHYSEMA IN FISCHER 344 RATS

Percutaneous absorption of [3H]tretinoin and systemic exposure to mequinol after dermal application of 2% mequinol/0.01% [3H]tretinoin (Solagé®) solution in healthy volunteers

Separation characteristics of molecular imprinted poly(methacrylic acid) for retinoid derivatives

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