RESUMEN
Carbamylation is a nonenzymatic post-translational modification observed during the reaction between cyanate and amino acids and/or proteins that may occur during some pathologies such as chronic kidney disease. Evidence suggests that carbamylation may interfere with the quantification of some analytes measured using immunoturbidimetric assays. C-reactive protein (CRP) is an inflammatory response protein that is commonly quantified through immunoturbidimetry in clinical laboratories. Because the presence of modified proteins in serum can lead to impaired quantification, this study aimed to verify the impact of in vitro carbamylation on the measurement of CRP in a CRP standard solution and serum pool. The samples were incubated with 150 nM, 150 µM, or 150 mM potassium cyanate (KOCN) or 20, 100, or 500 mg/dL urea at 37 °C for 24 h. CRP concentrations were measured using an immunoturbidimetric assay. The results showed a 61%-72% decrease in the CRP detection rate after incubation with KOCN. Incubation with urea resulted in a 0.7%-8% lower CRP detection rate. The results of this study indicate that high concentrations of cyanate can lead to falsely decreased CRP levels, as measured by immunoturbidimetry.
Asunto(s)
Proteína C-Reactiva , Carbamilación de Proteína , Humanos , Cianatos , UreaRESUMEN
The antipsychotic paliperidone was investigated with a focus on stability, degradation impurities and kinetics reaction profile. Osmotic tablets 3 mg (OROS® ) were subjected to extraction in an ultrasonic bath and the resulting acidic solution was stressed by forced conditions. Degraded samples were monitored by HPLC-DAD in different storage times for acidic and alkaline hydrolysis, oxidation, heat and photolysis. Photolysis was shown to be a strong degradation factor, with a drug content of 24.64% remaining after 24 h. Oxidation (H2 O2 18%) caused a slow decomposition, with a drug content of 83.49% remaining after 72 h. Through kinetics graphics, first-order reactions were found for oxidation, heat and photolysis. By UPLC-MS analysis, the degraded matrix could be investigated for identification of impurities with m/z 445.3128, m/z 380.8906, m/z 364.9391, m/z 232.9832 and m/z 217.0076, allowing the identification of derivatives N-oxide and with modifications in the lactam, benzisoxazole and pyrimidine rings. Paliperidone in liquid state, like analytical solutions or formulation, must be carefully handled to avoid drug exposure, specially in storage conditions.
Asunto(s)
Palmitato de Paliperidona/análisis , Palmitato de Paliperidona/química , Cromatografía Líquida de Alta Presión/métodos , Estabilidad de Medicamentos , Cinética , Espectrometría de Masas , Oxidación-Reducción , Fotólisis , ComprimidosRESUMEN
A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C18 column endcapped (50 × 4.0 mm, 2.0 µm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min-1 . Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC-MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of ß-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.