Degradation study of irbesartan: Isolation and structural elucidation of novel degradants

Mutha, V.V.S.R.N. Anji Karun; Guduru, Santhosh; Kaliyaperumal, Muralidharan; Rumalla, Chidananda Swamy; Maddi, Srinivasa Rao; Korupolu, Raghu Babu; Gajbhiye, Susheela Bai

doi:10.1016/j.jpba.2018.05.009

Cited by 9 publications

(5 citation statements)

References 10 publications

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“…As mentioned above, it was also identified as a degradant by Mutha and co-workers when studying the stability of IRB in 30% H 2 O 2 , 1 N HCl, and 1 N NaOH solutions at room temperature for 24 h. 14 Mechanochemically induced reactions followed by subsequent analysis of the residue allowed the identification of three additional major degradation products: IRB-3, IRB-4, and IRB-5 (Figure 5, Table S8-A). When IRB was reacted with oxone in the mixer mill for only 15 min, all three compounds were found.…”

Section: ■ Results and Discussionmentioning

confidence: 84%

“…13 On the other hand, Mutha et al demonstrated that IRB degrades under basic conditions and identified degradants with a cleaved imidazole moiety. 14 Shah and Singh revealed the formation of a δ-lactone after exposing a solution of TEL in 0.1 N HCl to light (13 days at 8500 lx and 0.05 W/m 2 ). 15 The light-induced degradation of VAL, which resulted in the loss of the carboxyl moiety, was studied by Bianchini and co-workers.…”

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confidence: 99%

“…Moreover, Rakibe and co-workers showed OLM degradation products with the loss of the 4-methyl-1,3-dixol-2-one moiety under acidic conditions . On the other hand, Mutha et al demonstrated that IRB degrades under basic conditions and identified degradants with a cleaved imidazole moiety . Shah and Singh revealed the formation of a δ-lactone after exposing a solution of TEL in 0.1 N HCl to light (13 days at 8500 lx and 0.05 W/m 2 ) .…”

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confidence: 99%

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Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions

Amer,

Backer,

Buschmann

et al. 2024

Anal. Chem.

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For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and costintensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. Highresolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15−60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.

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Section: ■ Results and Discussionmentioning

confidence: 84%

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confidence: 99%

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confidence: 99%

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Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions

Amer,

Backer,

Buschmann

et al. 2024

Anal. Chem.

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“…In the 1 benzene (the D ring), while the last one was attributed to the aldehyde proton H-11. Evidently, the starting product has undergone hydrolysis of the C-7/N-8 and N-8/C-9 bonds [27,28], along with the partial oxidation of carbon C-11 and the concomitant closure of a new six-term ring. The latter could result from an aromatic nucleophilic substitution reaction on the C-14 carbon of the previously chlorinated aromatic B-ring via the adjacent N-28 nitrogen of the tetrazole ring [29].…”

Section: Structural Elucidation Of Dbp7mentioning

confidence: 99%

Newly Discovered Irbesartan Disinfection Byproducts via Chlorination: Investigating Potential Environmental Toxicity

et al. 2023

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Irbesartan belongs to the Sartan family, whose members are used in the treatment of arterial hypertension and kidney disease among patients with hypertension and type 2 diabetes mellitus as part of a treatment based on antihypertensive drugs. This drug has reached surface waters, accumulating to the extent of being considered an emerging pollutant, along with other substances from the same class. Wastewater treatment plants, which constitute the main environmental source of this compound, fail to completely reduce its presence in wastewater and generate additional toxic byproducts through the chlorine-based disinfection process. This study provides a comprehensive investigation into the chlorination mechanisms of irbesartan, revealing the identity of twelve new byproducts, which were characterized using NMR and mass spectrometry (MS-TOF). The other six byproducts were published in a previous study, allowing for the confirmation of some aspects of the supposed mechanisms of degradation, along with the identification of those that had only been hypothesized. An ecotoxicological assessment of a mixture and isolated byproducts was performed using Raphidocelis subcapitata for algal growth inhibition, Daphnia magna for immobility, and Aliivibrio fischeri for luminescence inhibition. The results revealed the variable toxicity of irbesartan and its byproducts. Different organisms exhibited varying sensitivities to the byproducts, with Aliivibrio fischeri being the most sensitive. The coexistence of multiple byproducts in the environment, their high toxicity, and their potential interactions highlight the significant environmental risks associated with chlorination and its derivates. Our study highlights the ongoing debate surrounding the generation of disinfection byproducts.

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“…[8][9][10][11][12] It is a biphenyl tetrazole and an azaspiro compound, IUPAC name is 2-butyl-3- [4.4] non-1-en-4one. [13] Non-peptide angiotensin II receptor blockers (ARBs) are a class of medication used to treat heart failure and excessive blood pressure. [14] Longterm high blood pressure is the main risk factor for stroke or heart failure.…”

Section: Introductionmentioning

confidence: 99%

Novel Synthesis and Characterization of Irbesartan Derivative an Anti‐Hypertensive Active Pharmaceutical Ingredient (API)

Tomar,

Jayakumar,

Saxena

2024

Macromolecular Symposia

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The current research focuses on the design, method development, characterization, and clinical assessment of novel irbesartan medication compounds. The objective of synthetic modification of a drug molecule is to achieve the desired properties such as enhancing the pharmacological properties and minimizing the side effects. It is a biphenyl tetrazole and an aza‐spiro compound, a highly selective, potent nonpeptide compound that belongs to the sartan group, an authorized type‐1 angiotensin II receptor (AT1), dilates the blood vessels and is used in curing of to treat high blood pressure, cardiac arrest, and renal disease in diabetics. To achieve the structural modification of the irbesartan drug, the researcher prepared the FeCl3/SiO2 catalyst and successfully used it for the acetylation, chloro acetylation reaction of irbesartan with acetyl chloride and chloroacetyl chloride. Further, the reaction is performed in presence of the catalyst and without a catalyst to elucidate the role of the catalyst. With the aid of TLC, FT‐IR, and UV–visible spectral methods, the structural interpretation of synthesized derivatives is completed. The present work illustrates a novel method of synthesis of irbesartan derivatives through safe and convenient procedures. The pharmacological evaluation of synthetic derivatives and green chemistry protocol of synthesis is under progress.

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Degradation study of irbesartan: Isolation and structural elucidation of novel degradants

Cited by 9 publications

References 10 publications

Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions

Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions

Newly Discovered Irbesartan Disinfection Byproducts via Chlorination: Investigating Potential Environmental Toxicity

Novel Synthesis and Characterization of Irbesartan Derivative an Anti‐Hypertensive Active Pharmaceutical Ingredient (API)

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