ABSTRACT
A sensitive and accurate LC/MS method for the determination of elbasvir (ELB) and grazoprevir (GZP) in human plasma was established using daclatasvir (DCT) as an internal standard. The analytes were separated on a Waters Spherisorb phenyl column (150mm×4.6mm ID, 5µm particle size) maintained at 40°C±2°C. Gradient elution, at a flow rate of 0.8mLmin-1, was used. The mobile phase consists of 90% of acetonitrile mixed to 10% of a 5mM ammonium formate buffer (+0.1% v/v of trimethylamine, pH was adjusted to 3.2 by formic acid) as phase A and 10% of acetonitrile mixed to 90% of the same buffer as phase B. Liquid-liquid extraction with ethyl acetate solvent was used to recuperate compounds from plasma. The method was validated over a concentration range of 2 and 100ng/mL for GZP and between 1 and 50ng/mL for ELB. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<15%, and the accuracy values ranged from 94.2 to 107.8%. The robustness of the method was established using a two-level full factorial design.
ABSTRACT
To address sustainability issues, the green synthesis of nanomaterials has recently received considerable attention. This article addresses a novel and cost-effective adsorbent for the extraction of eight phenyl-N-methylcarbamate insecticides from water samples. We first synthesized a magnetite/hydroxyapatite nanocomposite using snail shell powder via an environmental friendly approach. The morphology and physicochemical properties of magnetic hydroxyapatite were characterized by Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. Magnetic extraction parameters were optimized using a Doehlert matrix. Under optimum conditions, the magnetic extraction coupled with a LC-MS method shows good linearity with R2 ≥ 0.9982, suitable intra- and interday precision, and limits of detection and quantification in the range of 0.052-0.093 µg/L and 0.11-0.31 µg/L, respectively. Satisfactory relative recoveries of all carbamates were achieved from fortified water samples in the range of 93.89-101.01%.
ABSTRACT
A new ultra-high-performance liquid chromatography method for the simultaneous quantification of sofosbuvir, daclatasvir and ledipasvir was developed. Two combinations of these direct-acting antivirals are used in hepatitis C virus infection therapy and show high efficacy and safety. Fractional factorial design was used for screening the most influential factors on separation and time analysis. These significant factors were optimized using a central composite design. The optimum resolution was carried out by using a Waters XBridge C18 column (150 mm, 4.6 mm ID, 5 µm) at a temperature of 35°C ± 2°C and acetonitrile/sodium perchlorate buffer (10 mM, pH = 3.2) (40: 60 v/v) as mobile phase at a flow rate of 1.5 mL min-1. UV detection was set at λ = 210 nm. A short chromatographic separation time was achieved. The developed method was validated according to the accuracy profile approach and was found specific, precise, faithful and accurate. The detection limits were between 0.07 and 0.13 µg mL-1. Hence, this novel method can be employed for the routine quality control analysis and in dissolution profile studies of generics containing these products.