A novel high-performance liquid chromatographic method combined with fluorescence detection for determination of ertugliflozin in rat plasma: Assessment of pharmacokinetic drug interaction potential of ertugliflozin with mefenamic acid and ketoconazole

Han, Dong-Gyun; Yun, Hwayoung; Yoon, In‐Soo

doi:10.1016/j.jchromb.2019.05.023

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…Plasma samples were pretreated using the solvent precipitation method, which is a rapid, simple, and inexpensive procedure compared to the solid phase or liquid–liquid extraction method (Gao et al, 2018). Acetonitrile has been widely used for the protein precipitation method (Ha et al, 2019; Han, Yun, et al, 2019) and was employed as a precipitating organic solvent in this study. To further improve the efficiency of the sample preparation procedure, several acids such as hydrochloride, acetic acid, and formic acid were tested.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations

Seo

Han

Baek

et al. 2023

Drug Development Research

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Alizarin (1,2-dihydroxyanthraquinone) is an anthraquinone reddish dye widely used for painting and textile dyeing. As the biological activity of alizarin has recently attracted increasing attention from researchers, its therapeutic potential as complementary and alternative medicine is of interest. However, no systematic research has been conducted on the biopharmaceutical and pharmacokinetic aspects of alizarin. Therefore, this study aimed to comprehensively investigate the oral absorption and intestinal/hepatic metabolism of alizarin using a simple and sensitive tandem mass spectrometry method developed and validated in-house. The present method for the bioanalysis of alizarin has merits, including a simple pretreatment procedure, small sample volume, and adequate sensitivity. Alizarin exhibited pHdependent moderate lipophilicity and low solubility with limited intestinal luminal stability. Based on the in vivo pharmacokinetic data, the hepatic extraction ratio of alizarin was estimated to be 0.165-0.264, classified as a low level of hepatic extraction. In an in situ loop study, considerable fractions (28.2%-56.4%) of the alizarin dose were significantly absorbed in gut segments from the duodenum to ileum, suggesting that alizarin may be classified as the Biopharmaceutical Classification System class II. An in vitro metabolism study using rat and human hepatic S9 fractions revealed that glucuronidation and sulfation, but not NADPHmediated phase I reactions and methylation, are significantly involved in the hepatic metabolism of alizarin. Taken together, it can be estimated that the fractions of oral alizarin dose unabsorbed from the gut lumen and eliminated by the gut and liver before reaching the systemic circulation are 43.6%-76.7%, 0.474%-36.3%, and 3.77%-5.31% of the dose, respectively, resulting in a low oral bioavailability of 16.8%. Therefore, the oral bioavailability of alizarin depends primarily on its chemical degradation in the gut lumen and secondarily on first-pass metabolism.

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Section: Resultsmentioning

confidence: 99%

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations

Seo

Han

Baek

et al. 2023

Drug Development Research

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“…The peaks of the analytes at the LLOQ should be discrete, identifiable, and reproducible with acceptable precision (<20%) and accuracy (within 80-120%). The extraction recovery, matrix effect, dilution integrity, and stability (under bench-top, freeze-thaw, post-preparative, and long-term conditions) in addition to the intra-assay (five different samples) and inter-assay (five different runs) precision and accuracy for each analyte were determined at the LLOQ and three different QC levels as described in the US FDA guidelines and in previous studies [11,[17][18][19]].…”

Section: Bioanalytical Methods Validationmentioning

confidence: 99%

“…However, some of these methods were not fully validated, used a large sample volume, and/or had drawbacks associated with sample preparation procedures such as liquid-liquid extraction and solid phase extraction, i.e., high cost, irregular recovery, and/or potential hazards associated with highly volatile solvents. Moreover, LC-MS/MS systems require high instrumentation and maintenance expenses, which may not be affordable for many institutions in resource-limited conditions [10,11]. In this regard, HPLC with fluorescence detection (HPLC-FL) methods can be a good alternative, because they are more accessible and cost effective than LC-MS/MS systems, and they generally offer better sensitivity and selectivity than HPLC-UV systems [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, a simple bioanalytical method using the HPLC-FL system was developed for the simultaneous quantitation of DUT and H-DUT in rat plasma and was validated for its original application to in vivo rat pharmacokinetic study on DUT. The potential of the pharmacokinetic drug interaction of DUT with KET ( Figure 1), an azole antifungal drug that is a potent CYP3A inhibitor [11,14], was investigated in terms of in vitro rat and human microsomal metabolism, in vitro protein binding, and in vivo rat pharmacokinetics. Approximately 50% of men aged over 50 years have pathological evidence of BPH and this number increases to >80% of men aged over 80 years [15].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Assessment of Metabolic Drug Interaction Potential of Dutasteride with Ketoconazole

et al. 2019

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Dutasteride (DUT) is a selective, potent, competitive, and irreversible inhibitor of both type-1 and type-2 5α-reductase (5AR) commonly used in the treatment of benign prostatic hyperplasia and androgenetic alopecia. In the present study, we developed a simple and sensitive high-performance liquid chromatography with fluorescence detection (HPLC-FL) method for simultaneous determination of DUT and its major active metabolite, 6β-hydroxydutasteride (H-DUT). Next, the pharmacokinetic interactions of DUT with ketoconazole (KET), a potent CYP3A inhibitor, were comprehensively investigated. In vivo rat intravenous and oral studies revealed that the pharmacokinetics of DUT and H-DUT were significantly altered by the co-administration of KET. Furthermore, the in vitro microsomal metabolism, blood distribution, and protein-binding studies suggest that the altered pharmacokinetics of DUT could be attributed primarily to the inhibition of the DUT metabolism by KET. To the best of our knowledge, this is the first study to show the drug interaction potential of DUT with azole antifungal drugs including KET, together with a newly developed HPLC-FL method for the simultaneous quantification of DUT and H-DUT.

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“…Qiu et al (Qiu et al 2019) published an UPLC-MS/MS method for simultaneous quantification of ERT and sitagliptin in rat plasma. Han et al (Han et al 2019) reported HPLC-fluorescence for determination of ERT in rat plasma with a linear range of 1-2000 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

Greenness Assessment of Spectrofluorometric Method for Quantification of Ertugliflozin: Application to Dosage Form and Human Urine.

Ahmed

2021

Records of Pharmaceutical and Biomedical Sciences

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The proposed work describes an ecofriendly, cost-effective, and sensitive spectrofluorometric method for the determination of ertugliflozin (ERT) in bulk material, pharmaceutical dosage form, and human urine. The method was developed by measuring the native fluorescence of the cited drug at λem= 334 nm after excitation at λex = 270 nm using water as a solvent. Different variables affecting the native fluorescence nature of ERT were successfully studied to obtain the optimum conditions of the proposed method. The assay was validated according to ICH guidelines for analytical and bioanalytical method validation and satisfactory results were obtained; percentage recoveries ranged between 99.47% and 101.36% and between 99.19 % and 101.90% upon analysis of ERT in dosage form and human urine respectively. No significant matrix effect was observed while measuring ERT in pharmaceutical dosage form or in human urine. The proposed method is considered the first spectrofluorometric method for quantification of ertugliflozin in dosage forms and human urine and can be applied to biological samples obtained from a pharmacokinetic study of ERT. Moreover, the method greenness was investigated by applying two different techniques and a comparative study was performed between the proposed method and other reported methods.

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A novel high-performance liquid chromatographic method combined with fluorescence detection for determination of ertugliflozin in rat plasma: Assessment of pharmacokinetic drug interaction potential of ertugliflozin with mefenamic acid and ketoconazole

Cited by 11 publications

References 31 publications

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations

In Vitro and In Vivo Assessment of Metabolic Drug Interaction Potential of Dutasteride with Ketoconazole

Greenness Assessment of Spectrofluorometric Method for Quantification of Ertugliflozin: Application to Dosage Form and Human Urine.

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