What is the difference between borneol and isoborneol

The mean total plasma clearance CL tot,p values of borneol were The mean distribution volumes at steady state V SS of borneol Borneol was not transformed to isoborneol in rats, which was indicated by the lack of isoborneol detected in plasma after the administration of Bingpian.

The use of herbal therapies is escalating worldwide. In correlating the administration of herbal medicines with their beneficial effects, it is important to understand the absorption, disposition, and pharmacokinetics of their active ingredients after dosing.

In addition to nonvolatile ingredients, many volatile constituents are also pharmacologically important for herbal therapies. However, the assays available for measuring volatile compounds have not been very successful in supporting the associated pharmacokinetic studies. Herein, we developed a reliable assay for the sensitive measurement of borneol, isoborneol, and their metabolite camphor in plasma to support a pharmacokinetic study of Bingpian. The high sensitivity of this assay was achieved by using a liquid-liquid microextraction technique in concert with PTV-based LVI of the organic extract for GC-MS, which was 33— times higher than the sensitivity of earlier reported analytical methods for Bingpian 27 , 28 , 29 , 30 , 31 , 32 , To our knowledge, this is the first time that liquid-liquid microextraction has been combined with PTV-based LVI and developed to measure the concentrations of volatile herbal compounds in complex biomatrices.

Our study provides a simple, effective solution to the analytical problem hampering the implementation of pharmacokinetic studies of herbal medicines containing volatile ingredients of pharmacological importance. Several liquid-liquid microextraction techniques such as single-drop microextraction, hollow fiber liquid phase microextraction, and dispersive liquid-liquid microextraction have been developed However, these techniques have some disadvantages, including tedious and labor-consuming operation, the requirement of special equipment, and applicability to a limited range of analytes.

Recently, Serrano et al developed a similar liquid-liquid microextraction combined with PTV-based LVI for water analysis to measure haloacetaldehyde concentrations in swimming pool water In this current study, the developed method of liquid-liquid microextraction combined with PTV-based LVI is quite feasible and can be routinely used for pharmacokinetic studies of Bingpian and the associated herbal products.

Our work is an important addition to previous studies associated with miniaturized liquid-liquid extraction techniques because we have addressed the application of this technique in the analysis of volatile and nonvolatile compounds, which could be predicted according to the analytes' log D and p K a.

Acute matrix-induced response enhancement has been observed for GC-based analyses of pesticide residues in fatty foods 34 , The matrix protects the analytes from both adsorption and alterations during transfer from the injector especially in the injection liner to the capillary column. The matrix effect results in the response of the analyte from a matrix sample being higher than that from a matrix-free solution containing the compound at the same concentration.

In this study, the acute matrix-induced response enhancement was almost negligible for the measurement of plasma concentrations of borneol, isoborneol, camphor, and the internal standard naphthalene. In addition, the compound responses and the chromatographic behaviors did not change significantly during and after successive injections of the plasma extract standard, indicating good tolerance of the PTV injector and the GC column for long-term use with plasma samples.

Borneol, isoborneol, camphor, and naphthalene are nonpolar and neutral compounds, which might explain the observed negligible matrix effects on the GC-MS-based measurement of the analytes. In summary, a reliable GC-MS-based assay for the sensitive measurement of plasma concentrations of borneol, isoborneol, and their metabolite camphor was developed, primarily by using liquid-liquid microextraction in concert with PTV-based LVI of the organic extract.

The application of the miniaturized liquid-liquid extraction technique could be extended to the measurement of other volatile compounds and many nonvolatile medicinal compounds in biomatrices, which can be predicted according to the log D and p K a of the analytes. On the basis of this newly developed assay, it was observed that, in rats, isoborneol was more likely to be metabolized into camphor than borneol.

Read article at publisher's site DOI : Front Pharmacol , , 04 May ChemCatChem , 13 9 , 10 Mar PeerJ , 8:e, 10 Jun Ann Transl Med , 8 6 , 01 Mar Molecules , 24 20 , 18 Oct To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation. Planta Med , 77 14 , 11 Apr Cited by: 3 articles PMID: J Sep Sci , 40 21 , 01 Nov Cited by: 1 article PMID: Biomed Chromatogr , 28 3 , 07 Oct Cited by: 6 articles PMID: J Sep Sci , 40 16 , 17 Jul Cited by: 0 articles PMID: Contact us.

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Search articles by 'Chen Cheng'. Cheng C 1 ,. Liu XW ,. Du FF ,. Li MJ ,. Fang Xu Search articles by 'Fang Xu'. Wang FQ ,. Yang Liu Search articles by 'Yang Liu'. Liu Y ,. Chuan Li Search articles by 'Chuan Li'.

Yan Sun Search articles by 'Yan Sun'. Sun Y. Affiliations 1 author 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. 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.

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.

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.

Free full text. Acta Pharmacol Sin. Published online Aug PMID: Author information Article notes Copyright and License information Disclaimer. Received May 4; Accepted Jun 5. This article has been cited by other articles in PMC. Go to:. 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.

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. 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.

Open in a separate window. Figure 1. Determination of analyte solubility Borneol, isoborneol, camphor, and the internal standard naphthalene, as well as a variety of nonvolatile compounds quercetin, ginkgolide A, orcinol glucoside, tanshinol, and cinnamic acid , were assessed for their solubility in phosphate buffered saline PBS; pH 7. Assessment of matrix effects on GC-MS-based assay The potential acute matrix-induced response enhancement 34 , 35 was assessed using a post-extraction spike method 36 , 37 for the PTV-based LVI involved in the GC-MS measurement of plasma levels of borneol, isoborneol, camphor, and the internal standard naphthalene.

Figure 2. Figure 3. Liquid-liquid microextraction enhances assay sensitivity Although n -hexane is an efficient solvent for extraction of borneol, isoborneol, camphor, and the internal standard naphthalene, evaporative losses of these volatile compounds when extracting from plasma occur upon the subsequent dry-down step.

Figure 4. Table 1 Physicochemical properties of borneol, isoborneol, camphor, and naphthalene, as well as those of quercetin, ginkgolide A, orcinol glucoside, tanshinol, and cinnamic acid. Assay reliability and sensitivity The potential acute matrix-induced response enhancement was assessed during assay development.

Table 3 Assay accuracy and precision relative standard deviation for the measurement of borneol, isoborneol, and camphor in rat plasma. Application of the novel assay in the pharmacokinetic study of Bingpian, synthetic Bingpian, and Fufang-Danshen tablets The pharmacokinetic study of Bingpian, synthetic Bingpian, and the synthetic Bingpian-containing phytopharmaceutical product Fufang-Danshen tablets in rats is an ideal application of the newly developed assay.

Figure 5. Table 4 Plasma pharmacokinetics of borneol, isoborneol, and camphor in rats receiving Bingpian, synthetic Bingpian, or Fufang-Danshen tablets. Aoshima H, Hamamoto K. Biosci Biotechnol Biochem. Common herbs, essential oils, and monoterpenes potently modulate bone metabolism.

This difference in polarity is due to the location of the hydroxyl group in borneol and isoborneol. Since the hydroxyl group is in the axial axis in borneol as opposed to the equatorial axis in isoborneol, it is further away from the two geminal methyl groups so it is more exposed to attraction with the polar solvent in the gas column.

The reaction is also seen as working when analyzing the IR spectra of the final product. As opposed to the camphor IR spectra, this product has an additional hydroxyl component in the IR.

Therefore, this demonstrates that the product has a hydroxyl component as in isoborneol and borneol. Even though there is still a carbonyl group in the IR, the reaction did not proceed to completion but based off of the hydroxyl component, the reaction still proceeded. This carbonyl group is the main difference between the lab data and literature data but this only means that the reaction did not go to completion but the reaction still proceeded.

Overall, this reduction reaction of camphor into isoborneol was completed relatively successfully. Even though the IR spectra of the final product includes a carbonyl group which is different than the literature, the reaction still proceeded in the reduction of camphor into isoborneol and borneol because of the hydroxyl peak.

The gas chromatography also shows evidence of the reaction proceeding when reducing camphor into borneol and isoborneol. The peak differences show that isoborneol was preferred over borneol, due to the steric strain caused by the two geminal methyl groups on one side of the cyclohexane. Since there is still a camphor peak on the gas chromatography spectra, the reduction reaction did not go to completion.

In future cases, this can be changed by including more sodium borohydride to reduce all the camphor and allow the reaction to proceed for a longer amount of time. In addition, osthole has beneficial effects in glioblastoma multiforme 4 , diabetes and acute ischemic stroke 5 , 6. Although osthole possesses many biological and pharmacological activities, the application of osthole in the clinic has been limited due to its poor bioavailability and low plasma concentration 7 , 8 , which results from rapid elimination by the CYP3A4 enzyme in the liver 9.

In addition, osthole is excreted in the kidneys and bile, which rely on the excretory function of P-glycoprotein A Chemical structures of osthole, borneol and isoborneol. Borneol, which is widely used in herbal medicine, is a component in the essential oils of numerous spice berries including Lavandula , Thymus vulgaris and Rosmarinus officinalis Linnaeus 11 — Borneol has additionally been used as a Chinese medicine exhibiting various bioactivities including sedation, anti-inflammation and antioxidant activity 14 — Previous studies have confirmed that borneol enhances the bioavailability of other drugs through pharmacokinetic interactions, including the intestinal absorption of salvianolic acid B and Akebia saponin 18 , 19 , the distribution of danshensu to the eye 20 and nasal absorption of geniposide In traditional Chinese medicine, co-administration of borneol with herbal drugs containing osthole, including Angelica pubescens , Fructus cnidii and Libanotis buchtormensis Fisch.

DC, was commonly used In addition, borneol inhibits cytochrome P enzyme, which participates in the elimination of osthole Collectively the evidence suggests that borneol may promote the bioavailability of osthole.

However, the pharmacokinetic interactions between osthole and borneol have not been reported. Shenzhen, China. Tongren, Guizhou, China. Jian, China. Standard osthole and paeonol were obtained from Chengdu Purechem-Standard Co. Chengdu, Sichuan, China. Chromatographic pure methanol, ethyl acetate and other chemicals and reagents were obtained from Guangzhou Lubex Biological Technology Co.

Guangzhou, Guangdong, China and were of analytical grade. Specificity: The specificity study was completed by comparing chromatograms of blank plasma, blank plasma spiked with osthole and IS, and plasma samples obtained from rats following oral administration. The calibration curve was structured by the peak area ratio Y of osthole to IS vs.

Accuracy and precision: Three quality control QC samples were used to test the accuracy and precision, with five replicates of each concentration. The measured concentrations were calculated using the calibration curves obtained daily. Inter-day precision and accuracy were evaluated by repeated analysis of the QC samples over 3 consecutive days. Extraction recovery: Extraction recovery was assessed by comparing the measured concentration vs.

Stability: The stability test was composed of a short-term, the freeze-thaw cycle and the long-term stability tests. The short-term stability test was performed by analysis of QC samples following storage at room temperature for 24 h. Freeze-thaw cycle stability was assessed following three freeze-thaw cycles within 3 consecutive days. All animals were fasted, with access to water only, for 12 h prior to drug administration. The dosage of borneol and osthole applied was based on that of a previous study Blood samples were collected at 5, 15, 30, 45, 60, 90, , , , and min following oral administration from the suborbital venous plexus of the rat eye socket vein.

Following blood collection, the animals were sacrificed following anesthesia. Pharmacokinetic analysis of osthole was performed based on a non-compartmental description of the data observed. The area under the plasma concentration-time curve AUC was calculated using the linear trapezoidal method. In addition, the maximum plasma concentration C max and the time to reach the maximum plasma concentration T max were obtained from the plasma concentration-time data.

Specificity: The typical chromatograms observed are depicted in Fig. There were no interference peaks near the retention time peaks of osthole 8.

Typical chromatograms of A blank plasma, B blank plasma spiked with osthole and C plasma samples 0. Chromatographic peaks: 1, Paeonol; and 2, osthole. Accuracy and precision: As presented in Table I , in the 3 QC samples, the intra-day precision ranged from 1. Analytical accuracy varied from The measured concentrations of osthole were calculated using the calibration curves obtained daily.

The spiked concentrations represent the concentration of the blank plasma spiked with osthole and internal solution. All of the results indicated that there was good repeatability of osthole following use as the sample pretreatment method.

SD, standard deviation; RSD, relative standard deviation. Stability: As presented in Table III , the percentage of remaining osthole in the three stability tests was between Results of short-term stability, freeze-thaw cycles and long-term stability of osthole analysis in rat plasma.