LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study

Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat blood, and reported their pharmacokinetic parameters. The chromatographic separation and detection of analytes were achieved within 4 min on ZORBAX SB-C8 (3.5 μm, 2.1 × 150 mm) column with gradient elution, and the flow rate was 0.25 mL/min. Simple protein precipitation was successfully applied for sample pretreatment. The HCQ displays a good linearity in the range of 2.0–5000.0 ng/mL, and the three metabolites also show good linearity ranging from 1.0 to 2500.0 ng/mL, with all correlation coefficients (R2) better than 0.98. In conclusion, this rapid, sensitive method was successfully developed, validated, and then applied to a pharmacokinetic study of HCQ in rat model in high dose. The results of the pharmacokinetic study presented an average half-life time 21.14 ± 10.31 h (mean ± SD) of HCQ, which is much shorter in human compared to that in mice. For the three metabolites, longer half-life times (approximately 100 h) were shown in rat.

Optical pH sensor based on polyelectrolyte complex (PEC) pectin-chitosan/methanol anthocyanin extract of Catharanthus roseus for a new optical urea biosensor development

Construction of optical pH sensor as a new platform optical urea biosensor based on polyelectrolyte complex (PEC) pectin-chitosan membrane and total phenolic (anthocyanin) of Tapak Dara flower (Catharanthus roseus) has been successfully carried out. The anthocyanin was extracted by a maceration method for 72 hours using methanol, and a total extract yield was 21.56% or 1.803 mg/L. Flavonoid and phenol tests showed positive results indicated by the formation of red and black colours. The anthocyanins showed maximum absorption at 578 nm for phosphate buffer and 575 nm for tris HCl buffer solution. The sensor fabrication was performed using a mixture of pectin and chitosan solutions with a ratio of 3:7. The anthocyanin was mixed into the solution with various concentrations. The sensor has an optimum sensitivity at the anthocyanin concentration of 0.05 mg/L (phosphate buffer) in the pH range of 7.0-9.5 and 0.025 mg/L (Tris HCl buffer) with a narrower pH range of 6.0-7.5. This sensor produced higher sensitivity, a wider linear range, and good linearity when it was exposed in 0.03M PBS. Reproducibility test with a relative standard deviation percentage (% RSD) was 9.20. The sensor showed a stable response after 5 minutes exposed to PBS solution, and it can be used to measure pH within the 20th day. The optimized optical pH sensor has been successfully developed as a urea optical biosensor by immobilizing urease on its surface. The biosensor showed a linear response in a series of 10-1-10-10 M urea concentrations and has good linearity.

Development, Optimization and Validation of a Sustainable and Quantifiable Methodology for the Determination of 2,4,6-Trichloroanisole, 2,3,4,6-Tetrachloroanisole, 2,4,6-Tribromoanisole, Pentachloroanisole, 2-Methylisoborneole and Geosmin in Air

Compounds 2,4,6-trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), 2,4,6-tribromoanisole (TBA) and pentachloroanisole (PCA), 2-methylisoborneol (2MIB) and geosmin (GSM) have been reported as being responsible for cork and wine taint. A sustainable method based on thermal desorption-gas chromatography–mass spectrometry (TD-GC/MS) has been developed and optimized, taking into account desorption parameters and chromatographic and mass spectrometric conditions. The combination of parameters that jointly maximized the compound detection was as follows: desorption temperature at 300 °C, desorption time at 30 min, cryo-temperature at 20 °C and trap high temperature at 305 °C. The proposed methodology showed a good linearity (R ≤ 0.994) within the tested range (from 0.1 to 2 ng) for all target compounds. The precision expressed as repeatability and reproducibility was RSD < 10% in both. The limits of quantification ranged from 0.05 to 0.1 ng. The developed methodology and the sampling rates (R-values) of all targeted compounds (from 0.013 to 0.071 m3 h−1) were applied to the air analysis of two wineries. The results showed that the developed methodology is a sustainable and useful tool for the determination of these compounds in air.

Magnetic Field Sensor Using Asymmetric Giant Magnetoimpedance Effect Created by Micro Magnets

A magnetic field sensor was developed using asymmetric giant magnetoimpedance (AGMI) effect. Amorphous ferromagnetic (Fe0.06Co0.94) 72.5Si12.5B15 wires were used in this study. The 2 cm long wire showed about 88 % and the 7 cm long wire showed about 197 % giant magnetoimpedance effect. When two micro magnets were placed 1 cm away from the ends of the wire, a distortion in two peak shapes of the GMI curve was observed and asymmetry was created by micro magnets and 7 cm long wire showed about 148 % AGMI effect. A simple and a new approach was designed to develop a magnetic field sensor, in the design circuit two signal generators were used to arrange linearity and dc offset in the output signal. The circuit output showed good linearity and zero hysteresis at ±250 A/m and ± 50 A/m magnetic field regions for 2cm wires long and 7 cm wires long, respectively.

Validation of an optimized HPLC/UV method for the quantification of flavonoids in lotus

Flavonoids present in the leaves of lotus (Nelumbo nucifera) grown in different regions of South Korea (Yeongcheon, Haenam, and Seocheon) and at different harvest times (July to September) were determined. Flavonoid contents in lotus extracts were identified and analyzed using high-performance liquid chromatography (HPLC). The HPLC results revealed that the flavonoid contents of the lotus extracts varied at different harvesting times, with the highest content in July. Analysis of the flavonoid content in the leaves from the different regions showed the highest contents of isorhamnetin-3-O-glucoside, quercetin 3-O-glucuronide, and quercetin 3-O-glucoside in Yeongcheon, Korea, and highest contnts of rutin, myricetin, kaempferol 3-O-glucoside, and quercetin in Haenam, Korea. The HPLC method was validated and optimized to quantify quercetin 3-O-glucuronide; it showed good linearity (1000–62.5 µg/mL, r2 = 0.9999), accuracy (106%–108%), and precision (RSD ≤ 1.70%). Determination of flavonoid content in lotus is valuable for producing medicinal crops and identifying the optimal sources to increase the quantity of clinically available medicines.

N-Nitrosodimethylamine Contamination in the Metformin Finished Products

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.

Enhancing the Linearity and Stability of a Fabric-Based Strain Sensor with Microfolded Graphene Structures

Fabric-based strain sensors can be seamlessly integrated into wearable systems for monitoring various physiological signals. Although many different approaches have been proposed to increase the sensitivity of the fabric-based strain sensor, the linearity and stability in large strains are still challenging. In this paper, a fabric-based strain sensor with good linearity and stability was fabricated via a three-step dip-coating method. Specifically, the combination of multiwall carbon nanotubes and reduced graphene oxide was used as the conductive material to enhance the stability. Meanwhile, microfolded structures between two reduced graphene oxide layers were created via pre-stretching to achieve good linearity. Through mechanical experiments, the performance of the fabric-based strain sensor was characterized. In addition, the practical applications of the strain sensor were demonstrated by monitoring different physiological signals.

Uv Spectrophotometric Methods for Determination of Sofosbuvir in Pure Form and Pharmaceutical Dosage Forms in Presence of Its Alkaline Degradate

Aims: Two spectrophotometric methods were developed and validated for the determination of sofosbuvir in presence of its alkaline degradate. Study Design: Ratio difference and ratio derivative methods were assisted for determination of sofosbuvir in presence of its alkaline degradate, laboratory-prepared mixtures and in tablet dosage forms. Place and Duration of Study: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy (Girls), Al - Azhar University, between December 2019 and January 2020. Methodology: Two analytical methods were achieved and validated for the quantitative determination of Sofosbuvir in presence of its alkaline degradate. The first method was ratio difference (RD) method, where the UV absorption spectra of different concentrations of sofosbuvir were divided by the spectrum of a certain concentration (15 µg mL-1) as a devisor of its alkaline degradate to get the ratio difference spectra. Afterwards, the peak amplitudes difference between 253.7 and 243.5 nm were measured. The second method was the ratio derivative (1DR) method, where the first derivative of the ratio spectra (1DR) was obtained and its amplitude was measured at 247 and 268 nm. Good linearity was obtained over the concentration range of 3-15 µg mL-1 for the proposed methods. The proposed procedures were adopted for the selective determination of intact Sofosbuvir in presence of up to 80% of its degradation product. Sofosbuvir was exposed to different conditions as alkaline, acidic and oxidative degradation. Results: The proposed methods were developed and validated with good linearity range of 3-15 µg mL-1 for both methods, and also with good accuracy and precision. And the obtained results were statistically compared to those obtained by the reported method. Conclusion: Sofosbuvir was successfully determined by the proposed ratio difference and ratio derivative methods in bulk powder, laboratory prepared mixtures and tablet dosage form with good accuracy and precision. The methods were validated according to ICH guidelines. The results obtained were compared with those of the reported method and were found to be in good agreement.