Abstract
Aim:
Both Borneolum (Chinese name Bingpian; dextrorotatory borneol) and Borneolum syntheticum (synthetic Bingpian; a mixture of optically inactive borneol and isoborneol) have been used for medicinal purposes in Chinese traditional medicine. The aim of this study was to develop a sensitive assay for measuring volatile ingredients borneol, isoborneol, and their metabolite camphor in pharmacokinetic study of Bingpian.
Methods:
Rat plasma samples were prepared using liquid-liquid microextraction: 70 μL of plasma sample (containing 125 nmol/L naphthalene as the internal standard) was extracted with 35 μL of n-hexane. The resulting n-hexane extract (20 μL) was introduced into a gas chromatography/mass spectrometry system using programmable temperature vaporizing-based large-volume injection. The assay was validated to demonstrate its reliability for the intended use. Using this assay, pharmacokinetic studies of Bingpian, synthetic Bingpian, and Fufang-Danshen tablets (containing synthetic Bingpian) were conducted in rats.
Results:
The extraction efficiency for the analytes and the internal standard from plasma was almost constant with decrease in n-hexane-to-plasma volume ratio, thus enabling a small volume of extracting solvent to be used for sample preparation, and enhancing the assay sensitivity. The lower quantification limit for measuring borneol, isoborneol, and camphor in plasma was 0.98 nmol/L, which was 33–330 times more sensitive than those reported earlier for Bingpian and synthetic Bingpian. The applicability of the miniaturized liquid-liquid extraction technique could be extended to measure other volatile and nonvolatile medicinal compounds in biomatrices, which can be predicted according to the analytes' octanol/water distribution coefficient (logD) and acid dissociation constant (pKa).
Conclusion:
This assay is sensitive, accurate and free of matrix effects, and can be applied to pharmacokinetic studies of Bingpian, synthetic Bingpian, and Bingpian-containing herbal products.
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References
Aoshima H, Hamamoto K . Potentiation of GABAA receptors expressed in Xenopus oocytes by perfume and phytoncid. Biosci Biotechnol Biochem 1999; 63: 743–8.
Mühlbauer RC, Lozano A, Palacio S, Reinli A, Felix R . Common herbs, essential oils, and monoterpenes potently modulate bone metabolism. Bone 2003; 32: 372–80.
Huang LS, Gu YF, Li H . Advances in herbal volatile oil and aromatic herbs. China J Chin Mater Med 2009; 34: 1606–11. Chinese.
Miguel MG . Antioxidant and anti-inflammatory activities of essential oils: a short review. Molecules 2010; 15: 9252–87.
Liang YZ, Xie PS, Chan K . Quality control of herbal medicines. J Chromatogr B 2004; 812: 53–70.
Li P, Qi LW, Liu EH, Zhou JL, Wen XD . Analysis of Chinese herbal medicines with holistic approaches and integrated evaluation models. Trends Anal Chem 2008; 27: 66–77.
Vogt W, Jacob K, Ohnesorge AB, Obwexer HW . Capillary gas chromatographic injection system for large sample volumes. J Chromatogr 1979; 186: 197–205.
Ŝtajnbaher D, Zupančič-Kralj L . Optimization of programmable temperature vaporizer-based large volume injection for determination of pesticide residues in fruits and vegetables using gas chromatography-mass spectrometry. J Chromatogr A 2008; 1190: 316–26.
“Zhonghua Bencao” Commission of State Administration of Traditional Chinese Medicine of the People's Republic of China. Zhonghua Bencao (Encyclopedia of Chinese Materia Medica); book 3. Shanghai: Shanghai Scientific and Technical Publishers; 1999. p 551–5 (natural Bingpian).
Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China (English Edition 2010); v 1. Beijing: China Medical Science Press; 2010. p 73–4 (natural Bingpian), 72–3 (synthetic Bingpian), and 684–6 (Fufang-danshen tablets).
Silva-Filho JC, Oliveira NNPM, Arcanjo DDR, Quitans-Júnior LJ, Cavalcanti SCH, Santos MRV, et al. Investigation of mechanisms involved in (−)-borneol-induced vasorelaxant response on rat thoracic aorta. Basic Clin Pharmacol Toxicol 2011; 110: 171–7.
Li YH, Sun XP, Zhang YQ, Wang NS . The antithrombotic effect of borneol related to its anticoagulant property. Am J Chin Med 2008; 36: 719–27.
Tian LL, Zhou Z, Zhang Q, Sun YN, Li CR, Cheng CH, et al. Protective effect of (±)isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells. Cell Physiol Biochem 2007; 20: 1019–32.
Liu R, Zhang L, Lan X, Li L, Zhang TT, Sun JH, et al. Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor ĸappaB signaling pathway. Neuroscience 2011; 176: 408–19.
Park TJ, Park YS, Lee TG, Ha HJ, Kim KT . Inhibition of acetylcholine-mediated effects by borneol. Biochem Pharmacol 2003; 65: 83–90.
Granger RE, Campbell EL, Johnston GAR . (+)- and (−)-borneol: efficacious positive modulator of GABA action at human recombinant α1β2γ2L GABAA receptors. Biochem Pharmacol 2005; 69: 1101–11.
Chen TF, Lin SG, Chen LX, Jiang GF, Liang ZY, Yang M, et al. Enhancement of absorption of tetramethylpyrazine by synthetic borneol. Acta Pharmacol Sin 1990; 11: 42–4.
Cheng G, Wu SR, Feng Y . Studies on the effects of borneol on the pharmacokinetics of rifampicin. J Shenyang Pharm Univ 2001; 18: 398–401. Chinese.
Liu QD, Liang MR, Chen ZX, Feng MR, Zhao P . The influence of borneol on the passing of gentamycin through blood-brain barrier. J Guangzhou College Tradit Chin Med 1994; 11: 37–40. Chinese.
Dong XZ, Tang XA, Qiu QH, Xu HB . Study on the auto-action of borneol assisting the penetration of DDP across BBB. Chin Pharm J 2002; 37: 275–7. Chinese.
Cai Z, Hou SX, Li YB, Zhao BB, Yang ZX, Xu SG, et al. Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration. J Drug Target 2008; 16: 178–84.
Jiang XF, Zou JL, Yuan YM, Law FCP, Qiao YJ, Yao MC . Preliminary study: biotransformation of borneol to camphor in mice, rats and rabbits. Mode Tradit Chin Med Mater Med 2008; 10: 27–36.
Manoguerra AS, Erdman AR, Wax PM, Nelson LS, Caravati EM, Cobaugh DJ, et al. Camphor poisoning: an evidence-based practice guideline for out-of-hospital management. Clin Toxicol 2006; 44: 357–70.
Lu T, Yang JY, Gao XM, Chen P, Du FF, Sun Y, et al. Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine. Drug Metab Dispos 2008; 36: 1578–86.
Liu HF, Yang JL, Du FF, Gao XM, Ma XT, Huang YH, et al. Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats. Drug Metab Dispos 2009; 37: 2290–8.
Hu ZY, Yang JL, Cheng C, Huang YH, Du FF, Wang FQ, et al. Combinatorial metabolism notably affects human systemic exposure to ginsenosides from orally administered extract of Panax notoginseng roots (Sanqi). Drug Metab Dispos 2013; 41: 1457–69.
Chen Q, Li SM, Wang W . GC-MS simultaneous determination of borneol and paeonol in mice plasma. Chin J Pharm Anal 2006; 26: 592–4. Chinese.
Huang TL, Ye SM, Ou WP, Mi SQ . Comparative study of the pharmacokinetics of borneolum syntheticum and borneol in herbal preparations. Tradit Chin Drug Res Clin Pharmacol 2006; 17: 265–7. Chinese.
Guo J, Huang X, Wang LL, Meng H, Zhang L, Ren P . Synchro-determination of borneol and tetramethyl pyrazine in plasma by GC-FID for volunteers administered with Suxiao Jiuxin Wan. Chin Tradit Herb Drugs 2003; 34: 730–2. Chinese.
Song HT, Guo T, Zhang XH, Kang J, Leng YX, Zhang RH . Determination of borneol in human plasma by capillary gas chromatography. Pharm J Chin PLA 2003; 19: 12–5. Chinese.
Xiao YY, Ping QN, Chen ZP . A simple gas chromatographic method for the simultaneous determination and pharmacokinetic study of tetramethylpyrazine phosphate and borneol in mouse plasma and brain tissue after oral administration of the Fufang tetramethylpyrazine phosphate tablets. J Chromatogr Sci 2008; 46: 395–400.
Xu XF, Li YB, Hou JP, Zhang SZ, Xu YY, Wang Y, et al. Pharmacokinetic study of borneol and menthol in rats after oral administration of qingyan drop pills. Planta Med 2011; 77: 1600–4.
Zhao JY, Lu Y, Du SY, Song X, Bai J, Wang Y . Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations. J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2012; 13: 990–6. Chinese.
Erney DR, Gillespie AM, Gilvydis DM . Explanation of the matrix-induced chromatographyic response enhancement of organophosphorus pesticides during open tubular column gas chromatography with splitless or hot on-column injection and flame photometric detection. J Chromatogr A 1993; 638: 57–63.
Poole CF . Matrix-induced response enhancement in pesticide residue analysis by gas chromatography. J Chromatogr A 2007; 1158: 241–50.
Matuszewski BK, Constanzer ML, Chavez-Eng CM . Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 2003; 75: 3019–30.
Guo B, Li C, Deng ZP, Chen SX, Ji ZH, Zhang JW, et al. A new method for measurement of (−)-sophocarpine, a candidate therapeutic for viral myocarditis, in plasma: application to a toxicokinetic study in beagle dogs. Rapid Commun Mass Spectrom 2005; 19: 2840–8.
Davies B, Morris T . Physiological parameters in laboratory animals and humans. Pharm Res 1993; 10: 1093–5.
Nováková L, Vlcková H . A review of current trends and advances in modern bio-analytical methods: chromatography and sample preparation. Anal Chim Acta 2009; 656: 8–35.
Serrano M, Salva M, Gallego M . Micro liquid-liquid extraction combined with large-volume injection gas chromatography-mass spectrometry for the determination of haloacetaldehydes in treated water. J Chromatogr A 2011; 1218: 8295–302.
Wang L, Sun Y, Du FF, Niu W, Lu T, Kan JM, et al. 'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting drug discovery pharmacokinetic study. Rapid Commun Mass Spectrom 2007; 21: 2573–84.
Acknowledgements
This study was financially supported by the National Natural Science Fundation of China for Distinguished Young Scholars (Grant 30925044), the National Basic Research Program of China (Grant 2012CB518403), and the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” (Grant 2009ZX09304-002).
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Cheng, C., Liu, Xw., Du, Ff. et al. Sensitive assay for measurement of volatile borneol, isoborneol, and the metabolite camphor in rat pharmacokinetic study of Borneolum (Bingpian) and Borneolum syntheticum (synthetic Bingpian). Acta Pharmacol Sin 34, 1337–1348 (2013). https://doi.org/10.1038/aps.2013.86
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DOI: https://doi.org/10.1038/aps.2013.86
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