Zirconium-based hydrophobic-MOFs as innovative electrode modifiers for flibanserin determination: Exploring the electrooxidation mechanism using a comprehensive spectroelectrochemical study.

Three different types of Zr-based MOFs derived from benzene dicarboxylic acid (BDC) and naphthalene dicarboxylic acid as organic linkers (ZrBDC, 2,6-ZrNDC, and 1,4-ZrNDC) were synthesized. They were characterized using X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), Fourier-transform IR spectroscopy (FT-IR), and Transmission electron microscopy (TEM). Their hydrophilic/hydrophobic nature was investigated via contact angle measurements; ZrBDC MOF was hydrophilic and the other two (ZrNDC) MOFs were hydrophobic. The three MOFs were combined with MWCNTs as electrode modifiers for the determination of a hydrophobic analyte, flibanserin (FLB), as a proof-of-concept analyte. Under the optimized experimental conditions, a significant enhancement in the oxidation peak current of FLB was observed when utilizing 2,6-ZrNDC and 1,4-ZrNDC, being the highest when using 1,4-ZrNDC. Furthermore, a thorough investigation of the complex oxidation pathway of FLB was performed by carrying out simultaneous spectroelectrochemical measurements. Based on the obtained results, it was verified that the piperazine moiety of FLB is the primary site for electrochemical oxidation. The fabricated sensor based on 1,4-ZrNDC/MW/CPE showed an oxidation peak of FLB at 0.8 V vs Ag/AgCl. Moreover, it showed excellent linearity for the determination of FLB in the range 0.05 to 0.80 µmol L-1 with a correlation coefficient (r) = 0.9973 and limit of detection of 3.0 nmol L-1. The applicability of the developed approach was demonstrated by determination of FLB in pharmaceutical tablets and human urine samples with acceptable repeatability (% RSD values were below 1.9% and 2.1%, respectively) and reasonable recovery values (ranged between 97 and 103% for pharmaceutical tablets and between 96 and 102% for human urine samples). The outcomes of the suggested methodology can be utilized for the determination of other hydrophobic compounds of pharmaceutical or biological interest with the aim of achieving low detection limits of these compounds in various matrices.

Polypyrrole/carbon dot nanocomposite as an electrochemical biosensor for liquid biopsy analysis of tryptophan in the human serum of normal and breast cancer women.

Liquid biopsy analysis represents a suitable alternative analysis procedure in several cases where no tumor tissue is available or in poor patient conditions. Amino acids can play a crucial role in aiding cancer diagnosis. Monitoring of tryptophan (Trp) catabolism can aid in tracking cancer progression. Therefore, a novel nanocomposite was fabricated using overoxidized polypyrrole film doped with nano-carbon dots (nano-CDs) on the pencil graphite electrode (PGE) surface for sensitive evaluation of Trp in human serum. Using square wave voltammetry (SWV), the overoxidized polypyrrole/carbon dots/pencil graphite electrode (Ov-Ox PPy/CDs/PGE) achieved excellent electrochemical catalytic activity for evaluating Trp. The modified electrode, known as Ov-Ox PPy/CDs/PGE, demonstrated superior electrochemical catalytic activity compared to bare PGE, CDs/PGE, PPy/PGE, and PPy/CDs/PGE for evaluation of Trp. The method's excellent sensitivity was confirmed by the low limits of detection (LOD = 0.003 µmol L-1) and limit of quantitation (LOQ = 0.009 µmol L-1). The biosensor that was developed can measure tryptophan (Trp) levels in the serum of both healthy individuals and female breast cancer patients with high accuracy and sensitivity. The results indicate that there is a significant difference, as shown by the F-test, between healthy individuals and those with breast cancer. This suggests that Trp amino acid could be an essential biomarker for cancer diagnosis. Consequently, liquid biopsy analysis presents a valuable opportunity for early disease detection, particularly for cancer.

A Comprehensive Review on Analytical Techniques for Determination of Sex Stimulants, PDE5 Inhibitors in Different Matrices with Special Focus on the Electroanalytical Methods.

Erectile dysfunction (ED) is one of the most common chronic diseases affecting men and its incidence increases with aging. Due to its substantial influence on the quality of life, phosphodiesterase type-5 (PDE5) inhibitors have been implemented to treat ED by increasing the penile blood flow that results in improving erection. PDE5 inhibitors is a class of drugs that affects many pharmacological sectors, and it is essential to review the different analytical methods described for their determination. Few reviews were published concerning this group of drugs. For this reason, this review article gathers the different analytical methods used to determine PDE5 inhibitors in pharmaceutical and biological samples over the past 20 years. Different analytical techniques were used to analyze these compounds in different matrices such as separation methods (capillary electrophoresis, LC-MS, UPLC-MS/MS, and GC-MS), spectroscopic methods (UV-visible methods, FT-IR spectroscopy and spectrofluorometry) and electrochemical methods (polarography, voltammetry and potentiometry). This review focuses on the different electrochemical methods and their use in analytical determination of PDE5 inhibitors in pharmaceutical dosage forms and biological samples. Moreover, it discusses the different modified electrodes used for their electroanalytical determination and the behavior of the studied drugs at different modified electrodes. Additionally, this review discusses the pharmacokinetics of the studied compounds and their interactions with other co-administered drugs especially the metabolic interactions between the studied compounds and other co-administered drugs in different matrices. This literature survey would provide a beneficial guide for future analytical investigation of PDE5 inhibitors.

Cytochrome P450 3A4-mediated pharmacokinetic interaction study between tadalafil and canagliflozin using high-performance thin-layer chromatography.

Diabetes is a known risk factor for sexual dysfunction in men; diabetic men have an increased risk of erectile dysfunction compared to non-diabetic men. Canagliflozin is one of the common antidiabetic drugs that is readily used in the treatment of type-2 diabetes. Concomitantly phosphodiesterase 5 inhibitors, such as tadalafil, can be given to the patient to alleviate erectile dysfunction. Canagliflozin is reported to be one of the cytochrome P450 3A4 enzyme inhibitors, that might seriously influence blood concentration levels of tadalafil but there is no study till now, discussing this interaction. Therefore, a fast, simple, and sensitive high-performance thin-layer chromatographic method was developed, validated, and applied for the simultaneous determination of tadalafil and canagliflozin in spiked and real human plasma. The limit of detection for tadalafil was 0.14 ng/band and for canagliflozin was 0.16 ng/band. The limit of quantitation value for tadalafil was 0.43 ng/band and for canagliflozin was 0.47 ng/band. Tadalafil and canagliflozin were determined simultaneously in real human plasma using the described procedure and the method was applied for in vivo pharmacokinetic drug interaction study between the studied drugs, which proved significant interaction between them when administered simultaneously.

Optimization of a sensitive and robust strategy for micellar electrokinetic chromatographic analysis of sofosbuvir in combination with its co-formulated hepatitis C antiviral drugs.

Based on our previous work with "pseudostationary-ion exchanger sweeping", we use this strategy to develop a sensitive, reliable and robust method for the analysis of the newly-FDA approved hepatitis C antiviral drugs namely; sofosbuvir (SOV), daclatasvir (DAC), ledipasvir (LED) and velpatasvir (VEP) in their pure forms and co-formulated pharmaceutical dosage forms using micellar electrokinetic chromatography (MEKC) as a separation method. For the first time, a successful separation of all the investigated compounds was achieved in less than 8 min using a basic background electrolyte (BGE) composed of 25 mmol L-1 SDS + 20% (v/v) ACN (acetonitrile) in 10 mmol L-1 disodium tetraborate buffer (final apparent pH is 9.90). A special focus was given to optimize the composition of the sample matrix to maintain the solubility of the analytes within the sample zone while gaining additional benefits regarding analyte zone focusing. It was found that replacing phosphoric acid (as a sample matrix) with a zwitterionic/isoelectric buffering compound (L-glutamic acid) has a substantial positive impact on the obtained enrichment efficiency. The interplay of other enrichment principles such as the retention factor gradient effect (RFGE) is also discussed. A full validation study is performed based on the pharmacopeial and ICH guidelines. The obtained limits of detection and quantitation are as low as 0.63 and 1.3 µg mL-1; respectively for SOV and DAC and 1.3 and 2.5 µg mL-1; respectively for LED and VEP using UV-DAD as a detection method. The selectivity of the developed method for determination of the studied compounds in their pharmaceutical dosage forms or in the presence of ribavirin (RIB) or elbasvir (ELB), which are other prescribed medications in the treatment regimen of patients with hepatitis C virus infection, is demonstrated. It is shown that with acidic sample matrix and basic BGE, an efficient and precise approach was designed in which analyte adsorption on the capillary wall was minimized while keeping repeatable peak height, peak area and migration time together with the highest possible enrichment efficiency.

In situ polymerization and FT-IR characterization of poly-glycine on pencil graphite electrode for sensitive determination of anti-emetic drug, granisetron in injections and human plasma.

In situ polymerization is a simple and efficient technique for modification and fabrication of modified electrodes in voltammetry. An efficient and highly sensitive square wave voltammetric (SWV) method was developed for analysis of a 5-HT3 antagonist granisetron (GRN) using in situ polymerized glycine on pencil graphite electrode surface. It was found that the fabricated polymer enhanced the sensitivity by more than two times and enhanced the surface activity by more than three times. Surface area measurements showed that poly-Gly/PGE have large surface area of 44.3 mm2, when compared to that of bare PEG (12.1 mm2). Several methods as cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) techniques were used to characterize the modified surface. Further, FT-IR spectroscopic study was used to predict the way of glycine polymerization on electrode surface and the possible interaction mechanism with GRN. After optimization, the proposed method showed a linear response of GRN concentrations in the range from 0.08 to 3.00 µmol L-1 with a limit of detection (LOD) of 26.2 nmol L-1 (9.14 ng mL-1). The method was utilized for GRN determination in ampoules and in real human plasma samples.

ε-MnO2-modified graphite electrode as a novel electrochemical sensor for the ultrasensitive detection of the newly FDA approved Hepatitis C antiviral drug ledipasvir.

A novel, simple and sensitive electrochemical method for the determination of ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed and validated using ε-MnO2-modified graphite electrode. Two different MnO2 polymorphs (γ- and ε-MnO2 nanoparticles) were synthesized and characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA). Surface area measurements show that ε-MnO2 NPs have large surface area of 345 m2/g, which is extremely high if compared to that of γ-MnO2 NPs (38 m2/g). In addition, a comprehensive study of the difference in the electrochemical behavior of LED while using pencil graphite electrode (PGE) modified with either γ- or ε-MnO2 NPs is carried out. It was found that surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors governing the sensitivity of the fabricated electrode toward the oxidation of the positively charged LED. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for the surface analysis of the modified electrodes. Based on the obtained results, ε-MnO2/PGE was applied as a selective and sensitive electrode for determination of LED. Under the optimized experimental conditions, ε-MnO2/PGE provides a linear response over the concentration range of 0.025-3.60 µmol L-1 LED with a low limit of detection, which was found to be 5.10 nmol L-1 (4.50 ng mL-1) for the 1st peak and 9.20 nmol L-1 (8.10 ng mL-1) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-IR and LC/MS. The fabricated sensor exhibits a good precision, selectivity and stability and was applied successfully for the determination of LED in its tablets and real rat plasma samples with a good recovery using a simple extraction technique.

Simultaneous TLC-densitometric determination of tamoxifen citrate and medroxyprogesterone acetate and UV-degradation kinetic study of medroxyprogesterone acetate.

Coadministration of tamoxifen citrate (TMC) and medroxyprogesterone acetate (MPA) is preferred to increase the response rate and the percentage recovery in patients with endometrial carcinoma. Administration of TMC and MPA and their combination affects estrogen and progestin receptor concentrations in advanced endometrium carcinoma by affecting 17ß-hydroxyl steroid dehydrogenase activity and serum hormone concentrations. A sensitive, accurate and robust thin-layer chromatography method has been established for simultaneous analysis of TMC and MPA. Method development was carried out on silica gel F254 using butanol-acetic acid-water (6:0.5:0.5, v/v/v) as mobile phase. Densitometric scanning was carried out at 241 nm for simultaneous detection of TMC and MPA. Retardation factor (Rf ) values for TMC and MPA were 0.21 and 0.85, respectively. The method was validated according to ICH guidelines. Regression plots revealed linear relationships in the concentration range of 50-500 and 25-250 ng/band for TMC and MPA, successively. Accuracy was ≥99.60 and 98.72% for TMC and MPA, respectively. Forced degradation studies using UV photodegradation was applied on MPA after exposure to UV light for different times and applying a kinetic study for calculating the degradation rate constant (k) and half-life time (t1/2 ).

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO2 nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples.

A novel MnO2 nanoparticles/chitosan-modified pencil graphite electrode (MnO2 NPs/CS/PGE) was constructed using two different MnO2 polymorphs (γ-MnO2 and ε-MnO2 nanoparticles). X-ray single phases of these two polymorphs were obtained by the comproportionation reaction between MnCl2 and KMnO4 (molar ratio of 5 : 1). The temperature of this reaction is the key factor governing the formation of the two polymorphs. Their structures were confirmed by powder X-ray diffraction (XRD), Fourier transform infrared (FTIR) and energy dispersive X-ray (EDX) analysis. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for surface analysis of the modified electrodes. Compared to bare PGE, MnO2 NPs/CS/PGE shows higher effective surface area and excellent electrocatalytic activity towards the oxidation of the standard K3[Fe(CN)6]. The influence of different suspending solvents on the electrocatalytic activity of MnO2 was studied in detail. It was found that tetrahydrofuran (THF) is the optimum suspending solvent regarding the peak current signal and electrode kinetics. The results reveal that the modified γ-MnO2/CS/PGE is the most sensitive one compared to the other modified electrodes under investigation. The modified γ-MnO2/CS/PGE was applied for selective and sensitive determination of FUR. Under the optimized experimental conditions, γ-MnO2/CS/PGE provides a linear response over the concentration range of 0.05 to 4.20 µmol L-1 FUR with a low limit of detection, which was found to be 4.44 nmol L-1 (1.47 ng mL-1) for the 1st peak and 3.88 nmol L-1 (1.28 ng mL-1) for the 2nd one. The fabricated sensor exhibits a good reproducibility and selectivity and was applied successfully for the determination of FUR in its dosage forms and in spiked urine samples with good accuracy and precision.