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Gas chromatographic-mass spectrometric analysis of perillyl alcohol and metabolites in plasma.
J Chromatogr B Biomed Sci Appl. 1999 May 14; 728(1):85-95.JC

Abstract

Perillyl alcohol (POH), a metabolite of d-limonene and a component of the lavender oil, is currently in Phase I clinical trials both as a chemopreventative and chemotherapeutic agent. In vivo, POH is metabolized to less active perillic acid (PA) and cis- and trans-dihydroperillic acids [DHPA, 4-(1'-methylethenyl)-cyclohexane-1-carboxylic acid]. Previous pharmacokinetic studies using a GC-MS method detected POH metabolites but not POH itself; thus these studies lacked information on the parent drug. The present report describes a sensitive GC-MS method for the quantitation of POH and metabolites using stable-isotopically labeled internal standards. The residue obtained from CH2Cl2 extraction of a plasma sample was silylated. The products were separated on a capillary column and analyzed by an ion-trap GC-MS using NH3 chemical ionization. POH-d3 was used as the internal standard for POH while 13C-PA-d2 was used as the internal standards for the metabolites. The quantitation limits for POH, PA, cis- and trans-DPA were <10 ng/ml using 1-2 ml plasma. The assay was validated in rat and human plasma. The assay was linear from 2 to 2000 ng/ml for POH, 10 to 1000 ng/ml for PA and trans-DHPA, and 20 to 1000 ng/ml for cis-DHPA monitored. The within-run and between-run coefficients of variation were all <8%. Preliminary pharmacokinetic data from a rat following i.v. administration of POH at 23 mg/kg and from a patient receiving POH at 500 mg/m2 p.o. was also provided. Intact POH, PA, cis- and trans-DHPA were all detected in plasma in both cases. Two new major metabolites were found in human and one in the rat plasma.

Authors+Show Affiliations

College of Pharmacy, Comprehensive Cancer Center, The Ohio State University, Columbus 43210, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10379660

Citation

Zhang, Z, et al. "Gas Chromatographic-mass Spectrometric Analysis of Perillyl Alcohol and Metabolites in Plasma." Journal of Chromatography. B, Biomedical Sciences and Applications, vol. 728, no. 1, 1999, pp. 85-95.
Zhang Z, Chen H, Chan KK, et al. Gas chromatographic-mass spectrometric analysis of perillyl alcohol and metabolites in plasma. J Chromatogr B Biomed Sci Appl. 1999;728(1):85-95.
Zhang, Z., Chen, H., Chan, K. K., Budd, T., & Ganapathi, R. (1999). Gas chromatographic-mass spectrometric analysis of perillyl alcohol and metabolites in plasma. Journal of Chromatography. B, Biomedical Sciences and Applications, 728(1), 85-95.
Zhang Z, et al. Gas Chromatographic-mass Spectrometric Analysis of Perillyl Alcohol and Metabolites in Plasma. J Chromatogr B Biomed Sci Appl. 1999 May 14;728(1):85-95. PubMed PMID: 10379660.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gas chromatographic-mass spectrometric analysis of perillyl alcohol and metabolites in plasma. AU - Zhang,Z, AU - Chen,H, AU - Chan,K K, AU - Budd,T, AU - Ganapathi,R, PY - 1999/6/24/pubmed PY - 1999/6/24/medline PY - 1999/6/24/entrez SP - 85 EP - 95 JF - Journal of chromatography. B, Biomedical sciences and applications JO - J. Chromatogr. B Biomed. Sci. Appl. VL - 728 IS - 1 N2 - Perillyl alcohol (POH), a metabolite of d-limonene and a component of the lavender oil, is currently in Phase I clinical trials both as a chemopreventative and chemotherapeutic agent. In vivo, POH is metabolized to less active perillic acid (PA) and cis- and trans-dihydroperillic acids [DHPA, 4-(1'-methylethenyl)-cyclohexane-1-carboxylic acid]. Previous pharmacokinetic studies using a GC-MS method detected POH metabolites but not POH itself; thus these studies lacked information on the parent drug. The present report describes a sensitive GC-MS method for the quantitation of POH and metabolites using stable-isotopically labeled internal standards. The residue obtained from CH2Cl2 extraction of a plasma sample was silylated. The products were separated on a capillary column and analyzed by an ion-trap GC-MS using NH3 chemical ionization. POH-d3 was used as the internal standard for POH while 13C-PA-d2 was used as the internal standards for the metabolites. The quantitation limits for POH, PA, cis- and trans-DPA were <10 ng/ml using 1-2 ml plasma. The assay was validated in rat and human plasma. The assay was linear from 2 to 2000 ng/ml for POH, 10 to 1000 ng/ml for PA and trans-DHPA, and 20 to 1000 ng/ml for cis-DHPA monitored. The within-run and between-run coefficients of variation were all <8%. Preliminary pharmacokinetic data from a rat following i.v. administration of POH at 23 mg/kg and from a patient receiving POH at 500 mg/m2 p.o. was also provided. Intact POH, PA, cis- and trans-DHPA were all detected in plasma in both cases. Two new major metabolites were found in human and one in the rat plasma. SN - 1387-2273 UR - https://www.unboundmedicine.com/medline/citation/10379660/Gas_chromatographic_mass_spectrometric_analysis_of_perillyl_alcohol_and_metabolites_in_plasma_ L2 - https://www.lens.org/lens/search?q=citation_id:10379660 DB - PRIME DP - Unbound Medicine ER -