Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with <i>β</i>‐glucuronidase and sufatase: a review of bio‐analytical methods

Ding, Yue; Peng, Ming; Zhang, Tong; Jiang, Tao; Cai, Zengxuan; Zhang, Yong

doi:10.1002/bmc.2912

Cited by 30 publications

(24 citation statements)

References 51 publications

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“…Generally, enzymatic and acid hydrolyses are 2 methods to obtain the free and conjugated forms of fl avonol. Unfortunately, for the acid hydrolysis method, the sample processing is under drastic conditions (heating at 70 °C for 1 h in a thermostatic water bath) thus unstable target analytes cannot always be quantifi ed accurately and completely, which is consistent with our preliminary study (data not shown) [ 30 ] . Therefore, enzymatic hydrolysis method was used to convert the conjugated metabolites into their free forms so that the total myricetin could be quantifi ed.…”

Section: ▼ Methods Developmentsupporting

confidence: 87%

Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

et al. 2013

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Myricetin is a widely distributed bioactive flavonoid with scientific interest attributed to its anti-oxidant, antitumor, and anti-inflammatory properties. A specific and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for identification and quantification of myricetin in rat plasma after oral and intravenous administrations. Kaempferol was used as an internal standard. Followed by β-glucuronidase and sulfatase hydrolysis and liquid-liquid extraction with ethyl acetate, the analytes were separated on an Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm) and analyzed in the selected ion recording with a negative electrospray ionization mode. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability and matrix effect. The assay was validated over a wide concentration range of 2-4,000 ng/mL. Intra- and inter-day precisions were all less than 13.49% and accuracy ranged from 95.75 to 109.80%. The present method was successfully applied to investigate a pharmacokinetic study of myricetin following intravenous and oral administrations to rats. The absolute bioavailability was found to be 9.62% and 9.74% at 2 oral doses (50 mg/kg and 100 mg/kg, respectively), which indicated myricetin was poorly absorbed after oral administration. To our knowledge, this is the first pharmacokinetic evaluation of myricetin as a single active pharmaceutical ingredient in preclinical studies.

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Section: ▼ Methods Developmentsupporting

confidence: 87%

Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

et al. 2013

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“…Moreover, we found sulfated and glucuronidated conjugates of ICT in rat plasma after intravenous administration, indicating that ICA II in rats can be metabolized without the aid of microbial flora in the colon. Sulfated and glucuronidated conjugates of ICT can be quantified using the hydrolysis method with β-glucuronidase and sulfatase [32]; we will present this research in a future paper.…”

Section: Resultsmentioning

confidence: 99%

Comparative Pharmacokinetics Study of Icariin and Icariside II in Rats

Tien

Zhang

et al. 2015

Molecules

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Abstract:To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-D-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03-1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra-and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats. The results indicated that 91.2% of ICA was transformed into ICA II after oral administration by rats, whereas only 0.4% of ICA was transformed into ICA II after intravenous administration. A comparison of the pharmacokinetics of ICA and ICA II after oral administration revealed that the C max and AUC 0´t of ICA II were 3.8 and 13.0 times higher, respectively, than those of ICA. However, after intravenous administration, the C max and AUC 0´t of ICA II were about only 12.1% and 4.2% of those of ICA. These results suggest that ICA and ICA II have distinct pharmacokinetic properties, and the insights obtained facilitate future pharmacological action studies.

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“…For the purpose of understanding metabolic pathways and overall metabolism of xenobiotics including polyphenolics such as curcumin, hydrolysis with glucuronidase and sulfatase enzymes may be used [47]. Furthermore, the application of enzymatic hydrolysis is useful when authentic reference standards of the conjugates are not available.…”

Section: Discussionmentioning

confidence: 99%

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study

Stohs

Chen

Preuss

et al. 2019

BMC Complement Altern Med

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BackgroundNumerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined.MethodsEight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis.ResultsHydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed.ConclusionsWhen enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products.Trial registrationClinicalTrails.gov, trial identifying number NCT04103788, September 24, 2019. Retrospectively registered.

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Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with β‐glucuronidase and sufatase: a review of bio‐analytical methods

Cited by 30 publications

References 51 publications

Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

Comparative Pharmacokinetics Study of Icariin and Icariside II in Rats

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study

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