Parallel artificial liquid membrane extraction coupled with UPLC-ESI-MS/MS method for high-throughput quantitation of repaglinide in diabetic patients.

A high-throughput therapeutic monitoring method was developed for repaglinide (RPG) in diabetic patients, combining parallel artificial liquid membrane extraction (PALME) with ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). PALME was performed using a 96-well donor plate comprising a donor solution containing a plasma sample, 50 mM phosphate buffer (pH = 8.0), and cetirizine (CTZ) as internal standard. A polypropylene (PP) porous membrane served as a selective support for the liquid membrane (SLM), preventing nonspecific binding produced by other membranes. The extraction was accomplished across SLM made of PP membrane with dodecyl acetate and 1 % trioctylamine (w/w), and the acceptor solution comprised DMSO and 200 mM formic acid (50:50, v/v). The simple workflow for PALME provided analyte enrichment, highly efficient sample cleanup, high throughput analysis, and excellent reproducibility. Method validation met FDA criteria, with a linear plasma calibration range (0.1-100 ng mL-1, r = 0.9995) and a lower limit of quantitation (LLOQ) of 0.1 ng mL-1. Recovery results at 98.9 % affirmed method reliability. The ability to analyze 198 samples per hour, coupled with a reduced amount of solvents, underscores the method's high throughput and eco-friendly profile. The PALME-UPLC-ESI-MS/MS method was successfully applied to therapeutic drug monitoring of RPG in diabetic patients following 2 mg RPG tablet administration, establishing its effectiveness.

Exploitation of multi-walled carbon nanotubes/Cu(ii)-metal organic framework based glassy carbon electrode for the determination of orphenadrine citrate.

Metal organic frameworks (MOFs), with structural tunability, high metal content and large surface area have recently attracted the attention of researchers in the field of electrochemistry. In this work, an unprecedented use of multi-walled carbon nanotubes (MWCNTs)/copper-based metal-organic framework (Cu-BTC MOF) composite as an ion-to-electron transducer in a potentiometric sensor is proposed for the determination of orphenadrine citrate. A comparative study was conducted between three proposed glassy carbon electrodes, Cu-MOF, (MWCNTs) and MWCNTs/Cu-MOF composite based sensors, where Cu-MOF, MWCNTs and their composite were utilized as the ion-to-electron transducers. The sensors were developed for accurate and precise determination of orphenadrine citrate in pharmaceutical dosage form, spiked real human plasma and artificial cerebrospinal fluid (ACSF). The sensors employed ß-cyclodextrin as a recognition element with the aid of potassium tetrakis(4-chlorophenyl)borate (KTpCIPB) as a lipophilic ion exchanger. The sensors that were assessed based on the guidelines recommended by IUPAC and demonstrated a linear response within the concentration range of 10-7 M to 10-3 M, 10-6 M to 10-2 M and 10-8 M to 10-2 M for Cu-MOF, MWCNTs and MWCNTs/Cu-MOF composite based sensors, respectively. MWCNTs/Cu-MOF composite based sensor showed superior performance over other sensors regarding lower limit of detection (LOD), wider linearity range and faster response. The sensors demonstrated their potential as effective options for the analysis of orphenadrine citrate in quality control laboratories and in different healthcare activities.

Utilization of a TiO2-CuO Bimetallic/Polyaniline Nanocomposite as a Transducer in a Solid Contact Potentiometric Sensor for the Determination of Vildagliptin.

Current fundamental electrochemical research shows the potential of utilizing polymeric nanostructured materials as ion-to-electron transducers. In this paper, aniline was polymerized in the presence of TiO2 and CuO nanoparticles to yield a bimetallic/PANI nanocomposite. It was applied as a transducer in a carbon paste electrode for the potentiometric determination of vildagliptin in the presence of 18-crown-6-ether as a recognition element. The electrode's potentiometric performance was studied according to the IUPAC guidelines. It exhibited a wide linearity range of 1 × 10-2 M to 1 × 10-8 M, remarkable sensitivity (LOD of 4.5 × 10-9 M), and a fast response time of 10 s ± 1.3. The sensor did not show any potential drift due to the absence of the water layer between the carbon paste and the metallic conductor. This endowed the sensor with high stability and a long lifetime, as 137 days passed without the need to change the carbon paste surface. The electrode was utilized for the determination of the concentration of vildagliptin in bulk, pharmaceutical tablets, and human plasma, with average recovery ranging from 97.65% to 100.03%.

The first spectrofluorimetric approach for accurate determination of trimetazidine in its dosage forms: Application to content uniformity testing.

A novel sensitive and simple spectrofluorimetric method has been developed then validated for the determination of trimetazidine in pure form and its tablets. This method is found on the reaction between trimetazidine's secondary amine moiety with NBD-Cl reagent, using borate buffer at pH 8.0 yielding a highly fluorescent product whose fluorescence intensity was measured at 526 nm (excitation at 466 nm). A calibration curve plotted showed that the linear range of the presented method was (50-700 ng/ml) with a correlation coefficient of 0.9998. The limits of detection (LOD) and limits of quantitation (LOQ) values were 15.01 and 45.50 ng/ml respectively. The presented approach was validated according to ICH guidelines and successfully applied for determining trimetazidine in its tablets with a mean percentage recovery of 99.65% ± 1.04, 99.23% ± 0.80 and 98.33% ± 1.03 for Metacardia® (20 mg), Vastor ® (20 mg) and Tricardia® (20 mg) tablets respectively. Finally, the proposed method was adopted to study the content uniformity test according to USP guidelines.

Dansyl azide as a selective fluorescence tagging probe for click chemistry reactions and its application to monitor rasagiline in pharmacokinetic studies.

Click chemistry has been widely used for bioorthogonal labeling of biomolecules for its high efficiency, regioselectivity and biocompatibility. In this study, dansyl azide (DNS-AZ) was introduced as a novel fluorescence labeling reagent for the determination of alkynes based on copper (I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry reaction. Rasagiline mesylate (RSM) is an irreversible, selective monoamine oxidase B (MAO-B) inhibitor. It is used as a model example for drugs with terminal alkyne moiety that could be monitored in biological samples with CuAAC reaction. RSM reacts with DNS-AZ in the presence of copper (II) and sodium ascorbate as catalysts to form stable 1,2,3-triazole derivative determined by HPLC with fluorescence detection. The developed methodology was optimized for sensitive and selective determination of RSM in rat plasma. Selegiline (SLG) was used as internal standard. The developed method was validated according to US-FDA guidelines in order to confirm method suitability for the intended application. The method allowed accurate and precise determination of RSM in the linearity range 0.50-100 ng mL-1 with a detection limit of 0.16 ng mL-1 for RSM in rat plasma. To confirm method applicability in real sample analysis, the developed method was employed to quantify RSM in a pharmacokinetic study in rats after administration of a single oral dose of RSM tablet.