A novel hydrophilic interaction liquid chromatography method for the analysis of arterolane; Isolation and structural elucidation of its major degradation product by LC-HRMS and NMR

Niguram, Prakash; Goswami, Ashutosh; Kate, Abhijeet S.

doi:10.1016/j.jpba.2020.113279

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…The peak of M8 was observed at 39.0 min with m/z 227.1761 [M + H] + (Figure S1, supporting information). The full MS and MS/MS spectra of M8 were similar to the degradation product (DP‐4) of ART for which the structure was confirmed by NMR 13 . Hence, the structure of M8 was proposed as N ‐(2‐amino‐2‐methylpropyl)‐2‐(4‐oxocyclohexyl) acetamide with elemental composition C 12 H 22 N 2 O 2 .…”

Section: Resultsmentioning

confidence: 67%

“…The probable reason could be the non‐availability of a suitable analytical method with sufficient retention and separation of the drug and its metabolites. We have published an analytical method with the desired retention of ART and associated degradation products recently 13 . In continuation, we have conducted in vitro and in vivo metabolite identification studies of ART as described here.…”

Section: Introductionmentioning

confidence: 99%

“…We have published an analytical method with the desired retention of ART and associated degradation products recently. 13 In continuation, we have conducted in vitro and in vivo metabolite identification studies of ART as described here. A total of 15 metabolites and their structural pathways have been predicted by tandem mass spectrometry (MS/MS) and accurate mass studies.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive metabolite identification study of arterolane using hydrophilic interaction liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry

Niguram

Kate

2022

Rapid Comm Mass Spectrometry

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In 2012, arterolane (ART) in combination with piperaquine received approval in India for the treatment of plasmodium-induced malaria; however, to date, a detailed metabolite identification study of ART has not been reported. Being polar in nature, ART shows early elution on reversed-phase columns which might be the rate-limiting factor of its systematic analytical studies. We have utilized hydrophilic interaction liquid chromatography (HILIC) to separate in vitro and in vivo metabolites of ART. Methods:The possible sites of metabolism were predicted by XenoSite software to obtain an initial assessment. In vitro studies were conducted by incubating the drug with liver microsomes such as human, rat and human S9 fractions. Later, in vivo studies were performed to check the metabolites in urine, faeces and plasma. The samples were pooled and subjected to the protein precipitation method before analysis by liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/QTOFMS). Results:We have observed 15 metabolites in this study which were phase I metabolites formed due to hydroxylation, dihydroxylation, peroxide bond scission and oxidation. Here, we report 11 metabolites of ART for the first time. The metabolic pathways and plausible structures were proposed according to accurate mass measurements and its MS/MS data. Conclusions:The present study comprehensively reports the in vitro and in vivo metabolism of ART mentioning 11 novel metabolites. Here, extensive use of HILIC has helped to efficiently separate various metabolites. These findings would help

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Section: Resultsmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive metabolite identification study of arterolane using hydrophilic interaction liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry

Niguram

Kate

2022

Rapid Comm Mass Spectrometry

Self Cite

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“…Initially, the UPLC-MS/MS method was developed with various mobile phase ratios comprising buffer and acetonitrile in the reverse-phase column. Finally, effective chromatographic separation of PZA and IS was observed on the Waters H-class UPLC (Waters, Milford, MA, USA) system with the BEH HILIC column (100 3 2.1 mm, 1.7 mm, Waters, Milford, MA, USA) [15]. The column temperature was maintained at 45 8C, and the injection volume was 2.0 mL.…”

Section: Analytical Methods Validationmentioning

confidence: 99%

Development and validation of UPLC-MS/MS method for in vitro quantitative analysis of pyrazinamide in lipid core-shell nanoarchitectonics for improved metabolic stability

Thalla

Jala

Borkar

et al. 2022

AChrom

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Pyrazinamide (PZA), a medication for tuberculosis, has high aqueous solubility and low permeability, undergoes extensive liver metabolism, and exhibits liver toxicity through its metabolites. To avoid this, PZA in lipid core-shell nanoarchitectonics has been formulated to target lymphatic uptake and provide metabolic stability to the incorporated drug. The UPLC-MS/MS method for reliable in vitro quantitative analysis of pyrazinamide (PZA) in lipid core-shell nanoarchitectonics as per ICH guidance was developed and validated using the HILIC column. The developed UPLC-MS/MS method is a simple, precise, accurate, reproducible, and sensitive method for the estimation of PZA in PZA-loaded lipid core-shell nanoarchitectonics for the in vitro determination of % entrapment efficiency, % loading of pyrazinamide, and microsomal stability of lipid core-shell nanoarchitectonics in human liver microsomes. The % entrapment efficiency was found to be 42.72% (±12.60). Lipid nanoarchitectonics was found to be stable in human liver microsomes, where %QH was found to be 6.20%, that is, low clearance. Thus, this formulation is suitable for preventing PZA-mediated extensive liver metabolism. These findings are relevant for the development of other lipid-mediated, suitable, stable nanoformulations containing PZA through various in vitro methods.

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An Inclusive Exploration of Forced Degradation Analysis of Some Therapeutic Categories of Drugs in the Last Decade

Narsinghani¹,

Tuteja²,

Singh³

2023

Journal of the Scientific Society

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In the pharmaceutical industry, forced degradation tests are used to assess the stability of drug samples. Examining degradation products under stress is beneficial for determining degradation pathways as well as designing and validating appropriate analytical techniques. Forced degradation experiments reveal the molecule’s chemical behavior, which aids formulation and packaging creation. The current review examines the forced degradation of a variety of therapeutic classes of medications, including anticancer, antihypertensive, antiviral, CNS pharmaceuticals, and other miscellaneous drugs. During forced degradation analysis, the study examines the degradation behavior of several medications from the abovementioned categories. The findings will likely aid researchers in determining the degradation process of related drugs belonging to the same category.

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A novel hydrophilic interaction liquid chromatography method for the analysis of arterolane; Isolation and structural elucidation of its major degradation product by LC-HRMS and NMR

Cited by 3 publications

References 17 publications

Comprehensive metabolite identification study of arterolane using hydrophilic interaction liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry

Comprehensive metabolite identification study of arterolane using hydrophilic interaction liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry

Development and validation of UPLC-MS/MS method for in vitro quantitative analysis of pyrazinamide in lipid core-shell nanoarchitectonics for improved metabolic stability

An Inclusive Exploration of Forced Degradation Analysis of Some Therapeutic Categories of Drugs in the Last Decade

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