Cleaning Efficiencies of Three Cleaning Agents on Four Different Surfaces after Contamination by Gemcitabine and 5-fluorouracile.

Occupational exposure to antineoplastic drugs has been documented for decades showing widespread contamination in preparation and administration areas. Apart from preventive measures, efficient cleaning of surfaces is indispensable to minimize the exposure risk. The aim of this study was to evaluate the efficiency of three cleaning agents after intentional contamination by gemcitabine (GEM) and 5-fluorouracile (5-FU) on four different surface types usually installed in healthcare settings. Glass, stainless steel, polyvinylchloride (PVC), and laminated wood plates were contaminated with 20 ng/µl GEM and 2 ng/µl 5-FU solutions. Wipe samples were analyzed for drug residues after cleaning with a) distilled water, b) aqueous solution containing sodium dodecyl sulfate (10 mM) and 2-propanol (SDS-2P), and c) Incides N (pre-soaked) alcoholic wipes. Quantification was performed by high-performance liquid chromatography (HPLC) for GEM and gas chromato-graphy-tandem mass spectrometry (GCMS/MS) for 5-FU. Recovery was determined and cleaning efficiency was calculated for each scenario. Mean recoveries were 77-89% for GEM and 24-77% for 5-FU and calculated cleaning efficiencies ranged between 95 and 100% and 89 and 100%, respectively. Residual drug amounts were detected in the range nd (not detected) - 84 ng GEM/sample and nd - 6.6 ng 5-FU/sample depending on surface type and cleaning agent. Distilled water and SDS-2P had better decontamination outcomes than Incides N wipes on nearly all surface types, especially for GEM. Regarding 5-FU, the overall cleaning efficiency was lower with highest residues on laminated wood surfaces. The tested cleaning procedures are shown to clean glass, stainless steel, PVC, and laminated wood with an efficiency of 89-100% after contamination with GEM and 5-FU. Nevertheless, drug residues could be verified by wipe samples. Pure distilled water and SDS in an alcoholic-aqueous solution expressed an efficient cleaning performance, especially with respect to GEM. The study results demonstrate the need to adapt cleaning procedures to the variety of drugs and surface types to develop effective decontamination strategies.

Concentrations of tenofovir and emtricitabine in saliva: implications for preexposure prophylaxis of oral HIV acquisition.

To prevent acquisition of HIV through oral sex, drugs used for preexposure prophylaxis (Prep) need to diffuse in saliva. We measured tenofovir (TFV) and emtricitabine (FTC) concentrations simultaneously in the plasma and saliva of 41 HIV-infected patients under stable antiretroviral treatment. Mean ratios of saliva/plasma concentration were 3% (±4%) and 86.9% (±124%) for TFV and FTC, respectively. Tenofovir disoproxil fumarate (TDF) should be used in combination with FTC to prevent oral acquisition of HIV.

Development and validation of a stability indicating isocratic HPLC method for gemcitabine with application to drug release from poly lactic-co-glycolic acid nanoparticles and enzymatic degradation studies.

OBJECTIVES: Previously reported HPLC methods for gemcitabine determination are time-consuming with complicated mobile phases and gradient elution. Thus, a sensitive and stability-indicating isocratic HPLC method, which provides simple, fast and precise measurements, was developed. This method was applied to study the digestive enzymatic degradation of gemcitabine, for the first time, and the protection afforded following incorporation into poly lactic-co-glycolic acid (PLGA) nanoparticles. METHODS: An analytical HPLC method was developed with an optimized combination of operating conditions. Forced degradation and application of the method to in-vitro drug release studies were conducted. Finally, gemcitabine-loaded nanoparticles were exposed to the digestive enzymes pepsin, trypsin and α-chymotrypsin, and the resulting degradation evaluated. KEY FINDINGS: The analytical method was linear between 1 and 100 µg/ml, with excellent accuracy of 99.91-101.77% and precision of 1.71 or lower, with a 0.014 µg/ml limit of detection (LOD) and a 0.043 µg/ml limit of quantification (LOQ). Following exposure of gemcitabine to stressors, the drug was relatively stable in strong acid (1 N HCl), base (1 N NaOH) and as an aqueous solution exposed to light over 7 days, with less than 10% degradation. However, gemcitabine was more susceptible to degradation at 70°C and oxidative conditions (3% v/v H2 O2 ) with greater than 10% degradation noted after 7 days. In-vitro drug release studies demonstrated a sustained drug release profile from PLGA nanoparticles, which also improved the resistance of gemcitabine to enzymatic degradation. CONCLUSION: These results demonstrate the utility and effectiveness of this simple isocratic HPLC method in evaluating the overall performance of a gemcitabine-loaded formulation.

Anticancer drug detection using a highly sensitive molecularly imprinted electrochemical sensor based on an electropolymerized microporous metal organic framework.

A simple and highly sensitive approach for the detection of the anti-neoplastic drug gemcitabine is presented, based on a one-step electropolymerized molecularly imprinted microporous-metal-organic-framework. The sensitive layer was prepared by electropolymerization of the aniline moieties of p-aminothiophenol- gold nanoparticles on the surface of gold electrodes tethered with p-aminothiophenol, in the presence of gemcitabine as a template molecule. Experimental parameters that control the performance of the sensor were investigated and optimized. Under optimal conditions a calibration curve was obtained in the linear range from 3.8 fM to 38 nM with a limit of detection of 3 fM. The obtained imprinted sensor has the advantages of easy manufacture, high sensitivity and selectivity and good reproducibility. Furthermore the feasibility of the proposed technique has been investigated on spiked serum samples and infusion solution containing gemcitabine.

Validated RP-HPLC method for the simultaneous analysis of gemcitabine and LY-364947 in liposomal formulations.

Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-ß1 receptor inhibitor, has shown promise for the treatment of fibrotic pancreatic cancer, by reducing collagen production and improving tumor drug penetration. The preparation and optimization of novel Gem and LY formulations, including co-encapsulation in liposomes, require a validated method for the simultaneous quantification of both drugs, a method that had yet to be developed. Here we demonstrate an RP-HPLC protocol for the simultaneous detection of Gem and LY at 266 and 228 nm with retention times of 3.37 and 11.34 mins, respectively. The method, which uses a C18 column and a KH2PO4 (10 mM)-methanol mobile phase, was validated for linearity, precision, accuracy, limits of detection, and robustness. Co-loaded liposomes with both Gem and LY (Gem/LY liposomes) were developed to investigate the protocol applicability to pharmacokinetic analysis and formulation characterization. The method specificity was evaluated in presence of liposomal components in fetal bovine serum (FBS). Finally, the method was demonstrated by quantifying Gem/LY liposomal encapsulation efficiency and concentration liposomes-spiked FBS.