The Role of Ranolazine in Heart Failure-Current Concepts

Kourampi, Islam; Katsioupa, Maria; Oikonomou, Evangelos; Tsigkou, Vasiliki; Marinos, Georgios; Goliopoulou, Athina; Katsarou, Ourania; Kalogeras, Konstantinos; Theofilis, Panagiotis; Tsatsaragkou, Aikaterini; Siasos, Gerasimos; Tousoulis, Dimitris; Vavuranakis, Manolis

doi:10.1016/j.amjcard.2023.09.066

Cited by 2 publications

(1 citation statement)

References 114 publications

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“…With the increasing clinical use of ranolazine, the need for precise and reliable quantification of this drug in biological matrices, particularly human plasma, has become paramount. 1,2 Accurate measurement of ranolazine concentrations in plasma is crucial for several reasons. First, ranolazine exhibits considerable interpatient variability in pharmacokinetics, necessitating individualized dosing to achieve therapeutic efficacy while minimizing side effects.…”

Section: Introductionmentioning

confidence: 99%

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

Farooq,

Khan

2023

IJPQA

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The present research outlines a comprehensive and systematic approach for the development and validation of a bioanalytical Liquid chromatography–mass spectrometry (LC-MS) method to quantify ranolazine in human plasma. The study employs principles of quality by design (QbD) to enhance method robustness, precision, and accuracy. The primary goals of this research were to create a reliable LC-MS method for the accurate quantification of ranolazine in human plasma and to validate this approach in accordance with established standards set by regulatory bodies. A secondary objective was to explore the application of QbD principles to optimize method performance. The study resulted in the successful development of an LC-MS method that exhibits exceptional specificity, sensitivity, accuracy, and precision in the quantification of ranolazine in human plasma. Specificity tests revealed no interference from endogenous plasma components. The method demonstrated good sensitivity with limit of quantitation (LoQ) of 5 ng/mL and limit of detection (LoD) of 2 ng/mL. Accuracy, as assessed through recovery studies, showed mean recoveries of 98, 99, and 101% for three different spiked concentrations. Precision, expressed as RSD, was below 5% for both intra-day and inter-day analyses. Linearity studies resulted in a calibration curve with an R² value of 0.9998. By employing QbD principles, the method demonstrated improved robustness, thus minimizing the impact of variability during sample analysis. Robustness experiments revealed minimal effects on precision and accuracy when varying critical parameters. This research not only presents a reliable LC-MS method for ranolazine quantification but also underscores the importance of incorporating QbD principles in bioanalytical method development. The validated method holds significant implications for clinical research, pharmacokinetic studies, and therapeutic drug monitoring. By enhancing the accuracy and robustness of ranolazine quantification, this method contributes to the advancement of pharmaceutical and clinical research, ultimately benefiting patient care and treatment outcomes.

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Section: Introductionmentioning

confidence: 99%

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

Farooq,

Khan

2023

IJPQA

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SIRT1 inhibitor EX-527 inhibits ventricular arrhythmias by selectively reducing late Na⁺ current in mice ventricular myocytes

Ma,

Liu,

Zhang

et al. 2024

BIO Web Conf.

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A significant aspect in causing arrhythmia in some pathological situations (e.g., myocardial ischemia, heart failure, etc.) is an increase in late sodium current (INaL) in ventricular myocytes; reduction of INaL is a novel target for heart failure therapy. Deacetylase SIRT1 has a variety of cardioprotective effects, but whether it exerts antiarrhythmic effects by inhibiting INaL remains to be studied. In previous experiments, it was found that SRT2104, a specific agonist of SIRT1, could inhibit INaL and ventricular arrhythmias induced by anemone toxin (ATX II). Furthermore, EX-527, a specific inhibitor of SIRT1, was used for the verification experiment, and it was found that EX-527 could also inhibit INaL, but there was no study of INaL by EX-527. In this study, whole-cell patch clamp technique and in vivo electrocardiogram recording were used to investigate the effect and mechanism of EX-527 (10 μM) on INaL in pathologically enlarged mouse ventricular myocytes such as ATX II (2 nM) or heart failure. The following are the study’s main findings: (1) EX-527 inhibited the ATX II-enhanced INaL (Fig. 1 A, B); (2) The inhibition of ATX II-enhanced INaL by EX-527 is stronger than that by SRT2104 (Fig. 1 C, E); (3) A combined inhibition of CaMKII and PKC nearly completely eliminated the effect of EX-527 to inhibit ATX II-enhanced INaL (Fig. 2); (4) EX-527 inhibited the TACenhanced INaL (Fig. 3); (5) EX-527 ended the protracted APD and got rid of all EADs brought on by ATX II (Fig. 4); (6) EX-527 dramatically decreased the frequency and length of ATX II-induced VT and VF (Fig. 5).

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The Role of Ranolazine in Heart Failure-Current Concepts

Cited by 2 publications

References 114 publications

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

SIRT1 inhibitor EX-527 inhibits ventricular arrhythmias by selectively reducing late Na⁺ current in mice ventricular myocytes

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The Role of Ranolazine in Heart Failure-Current Concepts

Cited by 2 publications

References 114 publications

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

SIRT1 inhibitor EX-527 inhibits ventricular arrhythmias by selectively reducing late Na+ current in mice ventricular myocytes

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SIRT1 inhibitor EX-527 inhibits ventricular arrhythmias by selectively reducing late Na⁺ current in mice ventricular myocytes