Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC-MS/MS.

Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH from the use of some legal medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate an LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine. Calibration curve range for both analytes was 1-128 ng/mL in oral fluid and plasma and 4-256 ng/mL in urine, being the lowest concentration the limit of quantification. Accuracy of the determined values of the target analytes for the five control levels ranged from 94.8 to 111.7% for oral fluid, from 91.3 to 100.2% for plasma and from 94.8 to 109.8% for urine. Imprecision for the five control levels did not exceeded 12.8% for oral fluid, 16.2% for plasma and 17.1% for urine. The method developed for the three matrices was validated and was also successfully applied to assess real samples, showing for the first time the detection of LDX in oral fluid.

A simple HPLC-DAD method for determination of adapalene in topical gel formulation.

A simple stability indicating high-performance liquid chromatography method for the analysis of adapalene in pharmaceutical gel formulation is developed and validated. An isocratic separation is performed using a Merck RP-8 (150 mm × 4.6 mm i.d., particle size 5 m) column and a mixture of acetonitrile water (67:33, v/v, pH adjusted to 2.5 with phosphoric acid) as the mobile phase. The detection is achieved with a photodiode array detector at 321 nm. The specificity of the method is verified by subjecting both the reference substance and the pharmaceutical form to hydrolytic, oxidative, photolytic, and thermal stress conditions. There is no interference from the excipients of the formulation on the determination of adapalene in gel. The response is linear over the concentration range of 8.0-16.0 µg/mL (r > 0.999) with a limit of detection and quantification of 0.04 and 0.14 µg/mL, respectively. The mean recovery is 100.8%. The RSD values for the intra- and inter-day precision studies are < 1.2%. The method is validated by reaching satisfactory results for linearity, selectivity, specificity, precision, accuracy, robustness, and system suitability.

Treatment of invasive fungal infections: stability of voriconazole infusion solutions in PVC bags

Voriconazole is a novel broad-spectrum antifungal drug, employed in the treatment of invasive fungal infections, and represents an alternative to amphotericin B treatment. The manufacturer recommends that any unused reconstituted product should be stored at 2ºC to 8ºC, for no more than 24 h, but no recommendations about i.v. infusion solutions are given. Previous works have reported on the stability of voriconazole in polyolefin bags and just one in 5 percent dextrose polyvinyl chloride (PVC) bags, at a 4 mg.mL-1 concentration. In this work, the stability of voriconazole as an i.v. infusion solution in 0.9 percent sodium chloride and in 5 percent dextrose, in PVC bags, at 0.5 mg.mL-1, stored at 4 ºC and at room temperature, protected from light, was evaluated. These infusion solutions were analyzed for a 21-day period. Chemical stability was evaluated by HPLC assay. Visual inspection was performed and pH of the solutions was measured. No color change or precipitation in the solutions was observed. The drug content remained above 90 percent for 11 days in 0.9 percent sodium chloride and for 9 days in 5 percent dextrose solutions. The i.v. infusion solutions stored at room temperature were not stable. At room temperature, the voriconazole content dropped down to 88.3 and 86.6 percent, in 0.9 percent sodium chloride or 5 percent dextrose solutions, respectively, two days after admixture. Assays performed at the end of the study suggest the sorption of voriconazole by the PVC bags. The results of this study allow cost-effective batch production in the hospital pharmacy.

Treatment of invasive fungal infections: stability of voriconazole infusion solutions in PVC bags.

Voriconazole is a novel broad-spectrum antifungal drug, employed in the treatment of invasive fungal infections, and represents an alternative to amphotericin B treatment. The manufacturer recommends that any unused reconstituted product should be stored at 2 masculineC to 8 masculineC, for no more than 24 h, but no recommendations about i.v. infusion solutions are given. Previous works have reported on the stability of voriconazole in polyolefin bags and just one in 5% dextrose polyvinyl chloride (PVC) bags, at a 4 mg.mL-1 concentration. In this work, the stability of voriconazole as an i.v. infusion solution in 0.9% sodium chloride and in 5% dextrose, in PVC bags, at 0.5 mg.mL-1, stored at 4 masculineC and at room temperature, protected from light, was evaluated. These infusion solutions were analyzed for a 21-day period. Chemical stability was evaluated by HPLC assay. Visual inspection was performed and pH of the solutions was measured. No color change or precipitation in the solutions was observed. The drug content remained above 90% for 11 days in 0.9% sodium chloride and for 9 days in 5% dextrose solutions. The i.v. infusion solutions stored at room temperature were not stable. At room temperature, the voriconazole content dropped down to 88.3 and 86.6%, in 0.9% sodium chloride or 5% dextrose solutions, respectively, two days after admixture. Assays performed at the end of the study suggest the sorption of voriconazole by the PVC bags. The results of this study allow cost-effective batch production in the hospital pharmacy.