Structural characterization of forced degradation products of empagliflozin by high resolution mass spectrometry

Niguram, Prakash; Kate, Abhijeet S.

doi:10.1080/10826076.2019.1625368

Cited by 11 publications

(7 citation statements)

References 15 publications

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“…The structure of EMPA-D15 might be due to the additional unsaturations in the structure of the parent drug molecule. In conclusion, the maximum degradants of EMPA were formed during acid hydrolysis, and the major ones were EMPA-D8 and EMPA-D9, generated due to the tetrafuran ring opening and elimination of the tetrahydrofuran ring, respectively [ 33 ].…”

Section: Gliflozins (Sglt2 Inhibitors)mentioning

confidence: 99%

“… Degradation pathways of empagliflozin (EMPA) in alkaline, oxidative and photolytic conditions; for EMPA-D15 and EMPA-D16 m / z [M+NH 4 ] + [ 32 , 33 , 49 ]. …”

Section: Figurementioning

confidence: 99%

“…The LC-UV method suitable for elucidating degradation of EMPA was also proposed by Niguram et al [33] using a Kromasil 100 C18 column from Merck and UV detection at 226 nm (Table 1). The sum of degradants generated during accelerated degradation was In the next study concerning EMPA [32], a simple and fast analytical method with a low limit of quantification was developed and validated to determine EMPA, its synthetic impurities, and its degradants.…”

Section: Chemical Degradation Of Gliflozins (Sglt2 Inhibitors) and Th...mentioning

confidence: 99%

Section: Chemical Degradation Of Gliflozins (Sglt2 Inhibitors) and Th...mentioning

confidence: 99%

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Metabolism and Chemical Degradation of New Antidiabetic Drugs: A Review of Analytical Approaches for Analysis of Glutides and Gliflozins

Gumieniczek

Berecka‐Rycerz

2023

Biomedicines

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The drug metabolism and drug degradation pathways may overlap, resulting in the formation of similar constituents. Therefore, the metabolism data can be helpful for deriving safe levels of degradation impurities and improving the quality of respective pharmaceutical products. The present article contains considerations on possible links between metabolic and degradation pathways for new antidiabetic drugs such as glutides, gliflozins, and gliptins. Special attention was paid to their reported metabolites and identified degradation products. At the same time, many interesting analytical approaches to conducting metabolism as well as degradation experiments were mentioned, including chromatographic methods and radioactive labeling of the drugs. The review addresses the analytical approaches elaborated for examining the metabolism and degradation pathways of glutides, i.e., glucagon like peptide 1 (GLP-1) receptor agonists, and gliflozins, i.e., sodium glucose co-transporter 2 (SGLT2) inhibitors. The problems associated with the chromatographic analysis of the peptide compounds (glutides) and the polar drugs (gliflozins) were addressed. Furthermore, issues related to in vitro experiments and the use of stable isotopes were discussed.

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Section: Gliflozins (Sglt2 Inhibitors)mentioning

confidence: 99%

“… Degradation pathways of empagliflozin (EMPA) in alkaline, oxidative and photolytic conditions; for EMPA-D15 and EMPA-D16 m / z [M+NH 4 ] + [ 32 , 33 , 49 ]. …”

Section: Figurementioning

confidence: 99%

Section: Chemical Degradation Of Gliflozins (Sglt2 Inhibitors) and Th...mentioning

confidence: 99%

Section: Chemical Degradation Of Gliflozins (Sglt2 Inhibitors) and Th...mentioning

confidence: 99%

See 2 more Smart Citations

Metabolism and Chemical Degradation of New Antidiabetic Drugs: A Review of Analytical Approaches for Analysis of Glutides and Gliflozins

Gumieniczek

Berecka‐Rycerz

2023

Biomedicines

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“…A detailed literature review reveals that a few analytical methods were reported for EGZ quantification using high‐performance liquid chromatography (Hanif et al, 2021; Mabrouk et al, 2019), high‐performance thin layer chromatography‐mass spectrometry (Bhole & Tamboli, 2018) in pharmaceutical dosage form, EGZ forced degradation, and impurity quantification using LC–MS methods (Chen et al, 2021; Manoel et al, 2020; Manoel et al, 2021; Niguram & Kate, 2019). The review also reported the simultaneous quantification of EGZ, metformin, and other active drug substances in formulation dosage forms (Abou‐Omar et al, 2021; Ayoub, 2015; Ayoub & Mowaka, 2017; van der Aart‐van der Beek et al, 2020; Wattamwar et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

A sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantification of assay and trace‐level genotoxic tosylate analogs (methyl and ethyl) in empagliflozin and its tablet dosage forms

Nakka,

Muchakayala,

Manabolu Surya

2023

Biomedical Chromatography

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This study performed the simultaneous quantification of assay and two alkyl sulfonate (tosylate) analogs of empagliflozin (EGZ), specifically methyl 4‐methyl benzene sulfonate (MMBS) and ethyl 4‐methyl benzene sulfonate (EMBS) in EGZ, and its finished dosage form using an accurate and sensitive ultra‐performance liquid chromatography‐mass spectrometry method. The separation was achieved on a Waters Acquity BEH Shield RP18 (100 × 2.1 mm, 1.7 μm) column in gradient elution mode with 0.1% formic acid and acetonitrile as the mobile phases and a flow rate of 0.5 mL/min. For simultaneous quantification, the multiple reaction monitoring technique was utilized. The procedure was successfully validated in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The peak areas of both impurities, along with their concentrations, exhibited a good relationship with Pearson's correlation coefficient (R), which was >0.999 in the range of 0.3–6 ppm with an EGZ concentration of 2 mg/mL. The percentage recoveries from the limit of quantitation (LOQ) to 200% to the specification level were in the range of 94.82%–102.92%, whereas the percentage relative standard deviation (%RSD) was <2. Therefore, this method is rapid and accurate to quantify MMBS, EMBS, and EGZ assay simultaneously from the marketed tablet dosage forms of EGZ for commercial release and stability sample testing.

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Development of a highly sensitive and eco-friendly high-performance thin-layer chromatography approach for the determination of empagliflozin, pioglitazone, and rosuvastatin simultaneously in pharmaceutical preparations and different biological fluids

El-Gizawy,

Atia,

Ali

et al. 2023

JPC-J Planar Chromat

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A simple, accurate, green and selective high-performance thin-layer chromatography (HPTLC) method has been developed and validated for the simultaneous estimation of empagliflozin, pioglitazone, and rosuvastatin in their synthetic ternary mixture and different biological fluids. These three drugs are used for the treatment of type 2 diabetes mellitus and dyslipidemia and have shown synergistic effects on cardiovascular outcomes. The ternary combination was separated on silica gel TLC plates G60 F254, utilizing a mixture of n-hexane‒ethyl acetate‒methanol‒glacial acetic acid in ratio (4.2:4:1.75:0.05, V/V) as a developing system using ultraviolet (UV) detection at 230 nm. All experimental parameters were optimized with a linearity range of 5‒250 ng per band for each drug, with good sensitivity and low limit of detection values reached, namely 1.72, 1.79, and 1.52 ng per band for empagliflozin, pioglitazone, and rosuvastatin, respectively. The developed method was applied for separation of the studied drugs in their synthetic ternary mixture and different biological fluids, with good recovery results ensuring high efficiency of the proposed approach. Eco scale, green analytical procedure index, and AGREE metric tools were used to evaluate the greenness of the proposed method.

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Structural characterization of forced degradation products of empagliflozin by high resolution mass spectrometry

Cited by 11 publications

References 15 publications

Metabolism and Chemical Degradation of New Antidiabetic Drugs: A Review of Analytical Approaches for Analysis of Glutides and Gliflozins

Metabolism and Chemical Degradation of New Antidiabetic Drugs: A Review of Analytical Approaches for Analysis of Glutides and Gliflozins

A sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantification of assay and trace‐level genotoxic tosylate analogs (methyl and ethyl) in empagliflozin and its tablet dosage forms

Development of a highly sensitive and eco-friendly high-performance thin-layer chromatography approach for the determination of empagliflozin, pioglitazone, and rosuvastatin simultaneously in pharmaceutical preparations and different biological fluids

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