Said A. Hassan

Abstract Antiepileptic drugs are among the most common medications that require therapeutic drug monitoring (TDM). Indeed, TDM provides a realistic approach to adjust drug doses for epilepsy based on plasma concentrations to optimize its clinical outcome. The most common technique for TDM is high-performance liquid chromatography, which has a very low green profile among analytical techniques. Perampanel (PER) is an inherently fluorescent compound that its fluorophore readily allows sensitive and quantitative measurements. This paper describes the development and validation of a sensitive, specific, and eco-friendly spectrofluorimetric method for the determination of PER. Experimental parameters affecting fluorescence intensity of the compound, including solvent dilution, temperature, and excitation wavelength, were studied and optimized. The developed spectrofluorimetric method was established in acetonitrile at ?ex =?295?nm and ?em =?431?nm over a concentration range of 5?60?ng/ml. The adopted method was applied for the determination of PER in human plasma; it was effective in the range of 15?50?ng/ml. The proposed method was found to be sensitive and specific for PER and can be applied successfully in TDM of PER and in quality control laboratories.

The presence of minor components represents a challenging problem in spectrophotometric analysis of pharmaceuticals. If one component has a low absorptivity or present in a low concentration compared to the other components, this will hinder its quantitation by spectrophotometric methods. Continuous Wavelet Transform (CWT) as a signal processing technique was utilized to figure out a solution to such a problem. A comparative study was established between traditional derivative spectrophotometry (Numerical Differentiation, ND) and CWT to indicate the advantages and limitations of each technique and possibility of solving the problem of minor components. A mixture of ibuprofen (IBU) and phenylephrine (PHE) with its degradation products forming a ternary mixture was used for comparing the two techniques. The two techniques were applied on raw spectral data and on ratio spectra data resulting in four methods, namely ND, CWT, Derivative Ratio-Zero Crossing (DRZC) and Continuous Wavelet Transform Ratio-Zero Crossing (CWTR-ZC) methods. By comparing the results in laboratory prepared mixtures, CWT technique showed advantages in analysis of mixtures with minor components than ND. The proposed methods were validated according to the ICH guideline Q2(R1), where their linearity was established with correlation coefficient ranging from 0.9995 to 0.9999. The linearity was in the range 3–40 μg/mL for PHE in all methods, while for IBU it was 20–180 and 30–180 μg/mL in CWT and ND methods, respectively. The CWT methods were applied for quantitative determination of the drugs in their dosage form showing the ability of the methods to quantitate minor components in pharmaceutical formulations.

Common antiepileptic drugs have complex pharmacokinetic characteristics leading to fluctuation in their plasma levels at the same therapeutic doses. Therefore, antiepileptic drugs turn out to be among the most common medications for which therapeutic drug monitoring (TDM) is crucial. Indeed, TDM provides a realistic approach to adjust drug doses in epilepsy care based on plasma concentrations to optimize its clinical outcome. Perampanel (PER) is an antiepileptic drug used for the treatment of primary generalized tonic-clonic seizures in combination with other drugs, such as carbamazepine (CAR). Drug-drug pharmacokinetic interactions are very common in this combination, which makes TDM of PER essential. A selective, accurate, and precise bioanalytical method has been developed for the simultaneous determination of PER and CAR in human plasma for the purpose of TDM. Liquid-liquid extraction using ethyl acetate was applied for sample preparation, and diazepam (DZP) was the internal standard. The adopted method could successfully determine PER and CAR within their cmax levels as the linearity range was 0.2–10 µg/mL for PER and 5–100 µg/mL for CAR. The chromatographic separation was achieved on a C8 column using acetonitrile, aqueous 0.1% glacial acetic acid (75 : 25, v/v) as a mobile phase in isocratic elution at a flow rate of 0.8 mL/min and an UV detection at 225 nm. The adopted method was validated according to EMA guidelines, and the results were within the acceptance criteria.

2-phenethylamine (PEA) is a prohibited trace amine, that possesses amphetamine-like effect and toxicity. However, it is still present in many weight loss dietary supplements on which the quantities of PEA are not always listed. Therefore, monitoring of this toxic compound in these hypothetically safe products is essential. Herein, PEA was assayed using ion-selective potentiometric membrane sensors. A novel combination of silver doped copper oxide (Ag/CuO) nanoparticles with 4-tert-butylcalix[8]arene (BCX8) was investigated as a new ion-to-electron transducer layer used with solid contact glassy carbon electrodes. To study the effect of this novel combination, three sensors were proposed based on the incorporation of plain sodium tetraphenylborate (TPB) ion exchanger (sensor 1), TPB with BCX8 only (sensor 2) and TPB with Ag/CuO nanoparticles and BCX8 (sensor 3). The doped metal oxide nanoparticles were prepared using a simple wet co-precipitation synthesis procedure and were characterized for particle shape and size, elemental composition, and optical band gap energy. Near Nernstian responses were achieved with slope values of 52.28 ± 0.45, 54.64 ± 0.98 and 55.34 ± 0.35 mV/concentration decade and LOD of 9.88 × 10−5, 7.18 × 10−5, and 9.77 × 10−6 M for sensors 1, 2 and 3; respectively. Sensor 3 showed linearity range 1 × 10−5 to 1 × 10−2 M and response time of 10 s. The Ag/CuO nanoparticles incorporated within BCX8 network provided improved electron transfer kinetics, and was found to provide the best sensitivity, widest linearity range and the most stable and fastest response among the compared sensors. The proposed sensors showed excellent percent recoveries when applied for the analysis of PEA in its multi-ingredient formulation and showed no statistical difference with the reported method.