Development and validation of liquid chromatography-electrospray-tandem mass spectrometry method for determination of flibanserin in human plasma: Application to pharmacokinetic study on healthy female volunteers.

A novel rapid and highly sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) bioanalytical method was established for the analysis of flibanserin in human plasma. Flibanserin d4 was used as internal standard (IS). Flibanserin and the internal standard (IS) were extracted from the plasma using protein precipitation technique with acetonitrile. A Kinetex C18 (2.6 µm, 2.1 × 50 mm) column was used for chromatographic separation and the mobile phase was a mixture of 20 mm ammonium acetate buffer (pH 4.5)-acetonitrile (50:50, v/v) with an isocratic elution mode and a flow rate of 0.3 mL/min. The analysis was performed on a Xefo TQD Waters mass spectrometer in multiple reaction monitoring mode with a positive electrospray ionization interface. The US Food and Drug Administration guidelines were followed during the bio-analytical methods validation regarding linearity, precision, accuracy, carryover, selectivity, dilution integrity and stability. The analysis run time was carried out within 2 min over a wide linear concentration range of 5-1000 ng mL-1 . Finally, the proposed method was successfully used in a pharmacokinetic study that measured flibanserin concentration in healthy, non-pregnant female volunteers after a single 100 mg oral dose of flibanserin.

Simultaneous determination of linezolid, meropenem and theophylline in plasma.

The data presented in this article are related to the research article entitled "Voltammeric monitoring of linezolid, meropenem and theophylline in plasma" (A.K. Attia, M.A. Al-Ghobashy, G.M. El-Sayed, S.M. Kamal, accepted in Anal. Biochem. 2018). This article describes a sensitive square wave voltammetric (SWV) method for simultaneous monitoring of linezolid (LIN), meropenem (MERO) and theophylline (THEO) in spiked plasma and in plasma of healthy volunteers.

Determination of voriconazole and co-administered drugs in plasma of pediatric cancer patients using UPLC-MS/MS: A key step towards personalized therapeutics.

Untreated invasive aspergillosis results in high mortality rate in pediatric cancer patients. Voriconazole (VORI), the first line of treatment, requires strict dose monitoring because of its narrow therapeutic index and individual variation in plasma concentration levels. Commonly co-administered drugs; either Esomeprazole (ESO) or Ondansetron (OND) have reported drug-drug interaction with VORI that should adversely alter therapeutic outcomes of the latter. Although VORI, ESO and OND are co-administered to pediatric cancer patients, the combined effect of ESO and OND on the plasma concentration levels of VORI has not been fully explored. In this study, an accurate, reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for simultaneous determination of VORI, ESO, and OND in ultra-low sample volumes (25 µL) of plasma of pediatric cancer patients. Based on the physicochemical properties of the studied drugs and internal standard, liquid-liquid extraction was successfully adopted with methyl t-butyl ether. Consistent and reproducible recovery of the three drugs and the internal standard were calculated using plasma and matrix matched samples (RE% > 72.97%, RSD < 8.29%). Chromatographic separation was carried out using UPLC with C18 column and a mobile phase of acetonitrile:water:methanol (70:25:5 V/V/V) at 0.3 mL/min. Mass spectrometric determination at positive electrospray ionization in the MRM mode was employed. The analysis was achieved within 4 min over a linear concentration range of 1.00-200.00 ng/mL for the three drugs. The assay validity was assessed as per the Food and Drug Administration guidelines for bioanalytical method validation, and satisfactory results were obtained. The accuracy and precision were within the acceptable limits for the three drugs in both quality control and incurred plasma samples. Matrix effect and process efficiency were investigated in neat solvent, post-extraction matrix, and plasma. Correlation of the plasma concentration levels of the three drugs revealed differences from the reported drug-drug interactions. This confirmed the need for simultaneous determination of VORI and co-administered drugs in order to achieve optimal therapeutic outcomes. To achieve this, analysis results of this study, genetic polymorphisms in CYP2C19 and clinical data will be used to establish one model incorporating all possible factors that might lead to variation in therapeutic outcomes.

Voltammetric monitoring of linezolid, meropenem and theophylline in plasma.

Treatment of healthcare associated Pneumonia (HCAP) caused by Methicillin-resistant Staphylococcus aureus (MRSA) requires therapeutic protocols formed of linezolid (LIN) either alone or in combination with meropenem (MERO) and theophylline (THEO). The inter-individual pharmacokinetic variations require the development of reliable therapeutic drug monitoring (TDM) tools especially in immunocompromised patients. A sensitive square wave voltammetric sensor using multiwalled carbon nanotubes (MWCNTs) modified carbon paste electrode in Britton-Robinson buffer was developed and validated. Experimental parameters such as pH, percentage of MWCNTs, and pre-concentration time were optimized. The sensor was employed at pH 11.0 for the determination of LIN in plasma within a concentration range of 2.5 × 10-8 - 8.0 × 10-6 mol L-1without interference from co-administered medications. On the other hand, simultaneous monitoring of LIN, MERO and THEO in plasma was feasible at pH 3.0 over concentration ranges of 4.0 × 10-7- 9.0 × 10-5, 8.0 × 10-7- 9.0 × 10-5 and 8.0 × 10-7 - 9.0 × 10-5 mol L-1, respectively. The performance of the proposed sensor was validated and the applicability for TDM has been demonstrated in plasma of healthy volunteers.

Voltammetric Assay of Metformin Hydrochloride Using Pyrogallol Modified Carbon Paste Electrode.

The electrooxidative behavior and determination of metformin hydrochloride, anti-hyperglycemic drug, on a pyrogallol modified carbon paste electrode were investigated using cyclic voltammetry and differential pulse voltammetry. Metformin hydrochloride shows an irreversible oxidation behavior over a wide interval of pH (Britton-Robinson buffers, pH 2-9). The peak current varied linearly in the range comprised between 8.0 × 10(-7) and 6.0 × 10(-6) mol/L with detection limit of 6.63 × 10(-8) mol/L and limit of quantification of 2.21 × 10(-7) mol/L. The method was proposed for the determination of metformin hydrochloride in dosage forms and urine.

Comparative study on the selectivity of various spectrophotometric techniques for the determination of binary mixture of fenbendazole and rafoxanide.

Five different spectrophotometric methods were applied for simultaneous determination of fenbendazole and rafoxanide in their binary mixture; namely first derivative, derivative ratio, ratio difference, dual wavelength and H-point standard addition spectrophotometric methods. Different factors affecting each of the applied spectrophotometric methods were studied and the selectivity of the applied methods was compared. The applied methods were validated as per the ICH guidelines and good accuracy; specificity and precision were proven within the concentration range of 5-50 µg/mL for both drugs. Statistical analysis using one-way ANOVA proved no significant differences among the proposed methods for the determination of the two drugs. The proposed methods successfully determined both drugs in laboratory prepared and commercially available binary mixtures, and were found applicable for the routine analysis in quality control laboratories.

Determination of antihypertensive drug moexipril hydrochloride based on the enhancement effect of sodium dodecyl sulfate at carbon paste electrode.

Herein, an electrochemical differential pulse voltammetric method was developed for the determination of moexipril hydrochloride based on the enhancement effect of sodium dodecyl sulfate. The oxidation process has been carried out in Britton-Robinson buffer. Moexipril hydrochloride exhibits a well-defined irreversible oxidation peak over the entire pH range (2-11). The peak current varied linearly over the range from 4.0 x 10(-7) to 5.2 x 10(-6) mol L(-1). The limits of detection and quantification were 6.87 x 10(-8) mol L(-1) and 2.29 x 10(-7) mol L(-1), respectively. The recovery was found in the range from 99.65% to 100.76%. The relative standard deviation was found in the range from 0.429% to 0.845%. The proposed method possesses high sensitivity, accuracy and rapid response. Finally, this method was successfully used to determine moexipril hydrochloride in tablets.