An HPLC Method for the Determination of Saxagliptin in Human Plasma with Fluorescence Detection

Tekkeli, Şerife Evrim Kepekçi; Kızıltaş, Mustafa Volkan; Dincel, Demet

doi:10.24297/jac.v5i3.2678

Cited by 4 publications

(1 citation statement)

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“…Chemically, Saxa, shown in Figure 1, is (1S, 3S, 5S)-2-((2S)-Amino (3-hydroxytricyclo (3.3.1.13,7) dec-1yl)acetyl)-2-azabicyclo(3.1.0) hexane 3carbonitrile [5]. Different techniques were reported in literature for determination of Saxa, including: liquid chromatography with tandem mass detection [6] [7,8], HPLC [9][10][11][12][13][14][15], HPLC with fluorescence detection [16], HPTLC [17], spectrophotometric and fluorometric detection [18]. A potentiometric method was also reported based on carbon paste electrode (CPE) modified with MwCNTs-CuO aminobenzo-18-crown-6-ether composite [19].…”

Section: Introductionmentioning

confidence: 99%

Design and application of molecularly imprinted electrochemical sensor for the new generation antidiabetic drug saxagliptin

et al. 2023

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Saxagliptin (Saxa) belongs to a new generation of antidiabetic pharmaceutical compounds used in combination with healthy diet and exercise to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). In this work, we report for the first time a molecularly imprinted polymer (MIP) based electrochemical sensor for the determination of Saxa. Computational calculations were performed, based on which five MIPs were synthesized using Saxa as a template, itaconic acid as a monomer, crosslinked with ethylene glycol dimethacrylate and Di methyl sulfoxide (DMSO) as a porogen with different ratios. Non‐covalent interaction (NCI) analysis has been also conducted, and the obtained isosurface analysis was used for graphical visualization of NCI that could occur in real space as well as for the discrimination between hydrogen bond interaction, Van Der Waals attraction and spatial repulsion. The optimized polymer was incorporated as a modifier for designing an electrochemical sensor comprising MIP and Multiwalled carbon nanotubes (MwCNT) within carbon paste electrode (CPE). The operational variables including incubation time, pH, scan rate, and accumulation time were optimized. The sensor showed linearity over the concentration range (1 × 10−9–1 × 10−15 M) with low limit of detection (LOD) 8 × 10−16 and 2 × 10−16 M on using DPV and EIS, respectively. The sensor was successfully applied for pharmaceutical formulations, urine, and human serum samples with recovery range between 97.45–100.64 %.

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Section: Introductionmentioning

confidence: 99%

Design and application of molecularly imprinted electrochemical sensor for the new generation antidiabetic drug saxagliptin

et al. 2023

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A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase‐4 (DPP4) inhibitor, utilized for the characterization of the drug

Suresh

Srinivas²,

Mullangi

2016

Biomedical Chromatography

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Inhibition of dipeptidyl peptidase-4 (DPP4) is an emerging therapeutic approach for treating type 2 diabetes and has revolutionized the concept of diabetes management. Sitagliptin is the first approved orally active, potent, selective and nonpeptidomimetic DPP4 inhibitor. Incidence of hypoglycemia and weight gain is negligible with sitagliptin treatment. It is used as monotherapy or in combination with other anti-diabetic drugs to treat type 2 diabetes. There are numerous bioanalytical methods published for the analysis of sitagliptin in preclinical and clinical samples. This review focuses on the various HPLC and LC-MS/MS methods that have been used to analyze sitagliptin in various biological matrices. A small section is devoted to the bioanalysis of other DPP4 inhibitors such as vildagliptin, saxagliptin and linagliptin. This review provides key information in a concise manner regarding sample processing options, chromatographic/detection conditions and validation parameters of the chosen methods for sitagliptin and other DPP4 inhibitors.

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Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure

Koyani

Kolesnik

Wölkart

et al. 2017

Biochemical Pharmacology

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Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca-ATPase 2a axis and Na-Ca exchanger function in Ca extrusion. This resulted in reduced sarcoplasmic reticulum Ca content, diastolic Ca overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure.

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An HPLC Method for the Determination of Saxagliptin in Human Plasma with Fluorescence Detection

Cited by 4 publications

References 0 publications

Design and application of molecularly imprinted electrochemical sensor for the new generation antidiabetic drug saxagliptin

Design and application of molecularly imprinted electrochemical sensor for the new generation antidiabetic drug saxagliptin

A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase‐4 (DPP4) inhibitor, utilized for the characterization of the drug

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure

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