Development, validation and application of the liquid chromatography tandem mass spectrometry method for simultaneous quantification of azilsartan medoxomil (TAK-491), azilsartan (TAK-536), and its 2 metabolites in human plasma

Kuze, Yoji; Kogame, Akifumi; Jinno, Fumihiro; Kondo, Takahiro; Asahi, Satoru

doi:10.1016/j.jchromb.2015.07.047

Cited by 8 publications

(5 citation statements)

References 17 publications

(17 reference statements)

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“…This is a great point which needs deep studies. In the present work, a reasonable mechanism of mass cleavage of sartans and related analogues (1)(2)(3)(4)(5)(6)(7)(8) is proposed in positive mode by ESI-MS n . A phenanthridin-6-amine ring could be formed by rearrangement.…”

Section: Introductionmentioning

confidence: 80%

“…Hence, preliminary information regarding the side products is helpful in evaluating any such effects during synthesis. An integrated approach on basis of HPLC‐ESI‐MS/MS technology was providing possibilities for the rapid and efficient detection and identification of impurities produced in the synthetic process . However, in previous communication, the information about the fragmentation characteristics of sartans is scanty for reference.…”

Section: Introductionmentioning

confidence: 89%

“…An integrated approach on basis of HPLC-ESI-MS/MS technology was providing possibilities for the rapid and efficient detection and identification of impurities produced in the synthetic process. [6][7][8] However, in previous communication, the information about the fragmentation characteristics of sartans is scanty for reference. Thus, insights into unimolecule dissociation are indispensable not only for illustrating the detailed mechanisms of gas-phase chemistry, but also for rapid and efficient identification of sartans.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, insights into unimolecule dissociation are indispensable not only for illustrating the detailed mechanisms of gas-phase chemistry, but also for rapid and efficient identification of sartans. In this study, we selected losartan (1), valsartan (2), irbesartan (3), omlesartan (4), azilsartan (5), azilsartan medoxomil (6), a degradation product of azilsartan medoxomil [2] (7) and a impurity of azilsartan (8) as research subjects and studied the fragmentation behavior of these sartans. The structures of compound 1-8 are shown in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

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Fragmentation studies of sartans by electrospray ionization mass spectrometry

Peng

et al. 2017

J. Mass Spectrom.

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Sartans and related analogues with 5-oxo-l, 2, 4-oxadiazole ring and tetrazole ring are investigated in detail using collision-induced dissociation (CID) method in positive ion mode by electrospray ionization tandem mass spectrometry (ESI-MS ). It is found that the protonated sartans and related analogues tend to form the N-substituted-3-substituted phenanthridin-6-amine ion which has a large conjugative structure. The possible fragmentation pathways were proposed for the first time, and the key structure of product ions was confirmed by high resolution tandem mass spectrometry and theoretical calculation. It is very helpful for understanding the intriguing roles of sartans analogues in fragmentation reactions and enriching the knowledge of the gas-phase chemistry of the oxadiazole and tetrazole ring. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fragmentation studies of sartans by electrospray ionization mass spectrometry

Peng

et al. 2017

J. Mass Spectrom.

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“…Urine samples were stored as 1-mL aliquots at approximately − 20 °C or lower. Concentrations of azilsartan, M-I, and M-II in plasma and urine were determined using validated liquid chromatography–tandem mass spectrometry assays at CMIC Laboratories, Nishiwaki, Japan [ 16 ]. For both the plasma and urine samples, 0.8 mol/L hydrochloric acid (20 μL) and methanol with internal standard (25 μL) were added to 100-μL samples for protein precipitation, followed by the addition of 0.1 mmol/L ammonium acetate buffer (pH 4.0; 500 μL).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label, Multicenter Study

et al. 2018

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IntroductionAzilsartan is an angiotensin II receptor blocker indicated for the treatment of patients with hypertension. The efficacy and safety of azilsartan are established in adults, but have not been evaluated in pediatric patients, nor has its pharmacokinetic profile been determined in pediatric patients.MethodsIn this phase 3, open-label, multicenter study, we investigated the pharmacokinetics and safety of single doses of azilsartan in six Japanese patients with hypertension, aged 9–14 years. The dose of azilsartan was 5 mg for three patients weighing less than 50 kg, with mean body weight at baseline of 27.5 kg, and 10 mg for three patients weighing at least 50 kg, with mean body weight at baseline of 65.9 kg.ResultsMean maximum plasma concentration (Cmax) of azilsartan was 888.3 and 831.3 ng/mL and median time to maximum concentration (Tmax) of unchanged azilsartan was 3.0 and 4.0 h, in the 5-mg and 10-mg groups, respectively. Mean areas under the plasma concentration–time curve (AUC) from 0–24 h post-dose (AUC0–24) and 0 h to infinity (AUC0–inf) were 6350.3 and 6635.7 ng h/mL, respectively, in the 5-mg group, and 6871.7 and 7433.3 ng h/mL, respectively, in the 10-mg group. Both doses were well tolerated; no treatment-emergent adverse events considered to be related to azilsartan occurred during the study.ConclusionOur data suggest that pediatric patients weighing less than 50 kg may have approximately 2-fold greater exposure to azilsartan than those weighing at least 50 kg at the same dose. Exposure to azilsartan in children weighing at least 50 kg is comparable to that in healthy adults at the same dose.Trial RegistrationClinicalTrials.gov identifier, NCT02451150.FundingTakeda Pharmaceutical Co. Ltd.

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