Juhaizah Talib

Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance

In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7μm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis.

Simultaneous determination of three organophosphorus pesticides in different food commodities by gas chromatography with mass spectrometry

A sensitive and selective gas chromatography with mass spectrometry method was developed for the simultaneous determination of three organophosphorus pesticides, namely, chlorpyrifos, malathion, and diazinon in three different food commodities (milk, apples, and drinking water) employing solid-phase extraction for sample pretreatment. Pesticide extraction from different sample matrices was carried out on Chromabond C18 cartridges using 3.0 mL of methanol and 3.0 mL of a mixture of dichloromethane/acetonitrile (1:1 v/v) as the eluting solvent. Analysis was carried out by gas chromatography coupled with mass spectrometry using selected-ion monitoring mode. Good linear relationships were obtained in the range of 0.1-50 μg/L for chlorpyrifos, and 0.05-50 μg/L for both malathion and diazinon pesticides. Good repeatability and recoveries were obtained in the range of 78.54-86.73% for three pesticides under the optimized experimental conditions. The limit of detection ranged from 0.02 to 0.03 μg/L, and the limit of quantification ranged from 0.05 to 0.1 μg/L for all three pesticides. Finally, the developed method was successfully applied for the determination of three targeted pesticides in milk, apples, and drinking water samples each in triplicate. No pesticide was found in apple and milk samples, but chlorpyrifos was found in one drinking water sample below the quantification level.

Development and validation of a rapid ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of darunavir, ritonavir, and tenofovir in human plasma: Application to human pharmacokinetics

A sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of darunavir, ritonavir and tenofovir in human plasma. Sample preparation involved a simple liquid-liquid extraction using 200 μL of human plasma extracted with methyl tert-butyl ether for three analytes and internal standard. The separation was accomplished on an Acquity UPLC BEH C18 (50 mm x 2.1 mm, 1.7 μm) analytical column using gradient elution of acetonitrile/methanol (80:20, v/v) and 5.0 mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4 mL/min. The linearity of the method ranged between 20.0 and 12 000 ng/mL for darunavir, 2.0 and 2280 ng/mL for ritonavir, and 14.0 and 1600 ng/mL for tenofovir using 200 μL of plasma. The method was completely validated for its selectivity, sensitivity, linearity, precision and accuracy, recovery, matrix effect, stability, and dilution integrity. The extraction recoveries were consistent and ranged between 79.91 and 90.04% for all three analytes and internal standard. The method exhibited good intra-day and inter-day precision between 1.78 and 6.27%. Finally the method was successfully applied for human pharmacokinetic study in eight healthy male volunteers after the oral administration of 600 mg darunavir along with 100 mg ritonavir and 100 mg tenofovir as boosters.

Synthesis of visible light active doped TiO2 for the degradation of organic pollutants—methylene blue and glyphosate

BackgroundA simple hydrothermal process was applied to synthesize the doped TiO2 particles with different concentrations as well as different metal ions (Mn, Ce and La).MethodsThe synthesis of Mn-doped-TiO2 nanoparticles was done by using a hydrothermal method from hydrolysis of titanium tetrachloride in aqueous solution. The photocatalytic activities were checked by studying the degradation of two model organic pollutants.ResultsThe material was characterized by X-ray diffraction, scanning electron microscopy, and UV–Visible spectroscopy. The X-ray diffraction pattern studied for doped TiO2 particles suggests the anatase phase with a crystalline nature. Doped TiO2 particles showed a porous and complex nature with a highly rough surface. The photocatalytic activity of Mn- Ce- and La-doped TiO2 with different metal-ion concentrations of 0.15-0.60% show that the degradation rate of all of the pollutants increases with an increase in the dopant concentration from 0.15 to 0.45%, and a further increase in the dopant concentration decreased the degradation rate.ConclusionsThe results indicate that TiO2 with a concentration of 0.45% for all metal ions (Mn, Ce and La) shows the highest activity. Among studied dopent TiO2 with Mn (0.45%) showed the best degradation activity.