Simple laccase-based biosensor for formetanate hydrochloride quantification in fruits

This work describes the development of an electrochemical enzymatic biosensor for quantification of the pesticide formetanate hydrochloride (FMT). It is based on a gold electrode modified with electrodeposited gold nanoparticles and laccase. The principle behind its development relies on FMT's capacity to inhibit the laccase catalytic reaction that occurs in the presence of phenolic substrates. The optimum values for the relevant experimental variables such as gold nanoparticles electrochemical deposition (at − 0.2 V for 100 s), laccase immobilization (via glutaraldehyde cross-linking), laccase concentration (12.4 mg/mL), substrate selection and concentration (5.83×10−5 M of aminophenol), pH (5.0), buffer (Britton–Robinson), and square-wave voltammetric parameters were determined. The developed biosensor was successfully applied to FMT determination in mango and grapes. The attained limit of detection was 9.5×10−8 ± 9.5×10−10 M (0.02 ± 2.6×10−4 mg/kg on a fresh fruit weight basis). Recoveries for the five tested spiking levels ranged from 95.5 ± 2.9 (grapes) to 108.6 ± 2.5% (mango). The results indicated that the proposed device presents suitable characteristics in terms of sensitivity (20.58 ± 0.49 A/μM), linearity (9.43×10−7 to 1.13×10−5 M), accuracy, repeatability (RSD of 1.4%), reproducibility (RSD of 1.8%) and stability (19 days) for testing of compliance with established maximum residue limits of FMT in fruits and vegetables.

EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

In vitro compatibility of remifentanil hydrochloride and sufentanil citrate with selected drugs

: Objectives Physicochemical incompatibilities between intravenous drugs are a recurrent problem in intensive care units. The present study was aimed at investigating the physical compatibility of remifentanil and sufentanil with other drugs (insulin, midazolam, propofol, potassium chloride, magnesium sulfate, furosemide, heparin, monobasic potassium phosphate) that are frequently administered together intravenously. In addition, the physicochemical compatibility of three common associations of drugs was evaluated in glass tube tests and during dynamic simulated Y site administrations (remifentanil-insulin-midazolam; remifentanil-insulin-propofol; sufentanil-insulin-midazolam). Methods Physical compatibility was verified by visual inspection of the various mixtures (two, three or four drugs) in glass tubes and by pH determination of the mixtures collected during simulated Y site administrations. Solutions were considered as compatible in the absence of any visual change in the solution and of any significant variation in pH value. In addition, chemical stability was checked during in vitro dynamic simulations. The solutions were prepared in 50 ml syringes, placed on syringe pumps and connected to a Swan-Ganz catheter; the liquid collected at the tip was assayed by high performance liquid chromatography. Results In the visual examinations, only the associations of remifentanil and furosemide were incompatible. The three assayed associations were compatible in the tested proportion range over 24 h. Conclusions Remifentanil was physically compatible with the tested drugs, except for furosemide (Lasix; Sanofi-Aventis, 250 mg/25 ml) and physicochemically compatible with insulin and midazolam and insulin and propofol. Sufentanil was physically compatible with all tested drugs and physicochemically compatible with insulin and midazolam

Place de ta vitamine D, du sevelamer et du cinacalcet dans la prise en charge des patients en insuffisance rénale [Treatment of secondary hyperparathyroidism in renal insufficiency: role of calcitriol, sevelamer and cinacalcet]

Along with the decrease in kidney function arises a secondary hyperparathyroidism, which constitutes one of the most important risk factor for mortality in patients suffering from renal insufficiency. Treating secondary hyperparathyroidism is challenging, as most of the parameters of mineral metabolism are interconnected. We review here the pathophysiology and treatment options of this entity.

Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Development and validation of a dissolution test for diltiazem hydrochloride in immediate release capsules

This work describes the development and validation of a dissolution test for 60 mg of diltiazem hydrochloride in immediate release capsules. The best dissolution in vitro profile was achieved using potassium phosphate buffer at pH 6.8 as the dissolution medium and paddle as the apparatus at 50 rpm. The drug concentrations in the dissolution media were determined by UV spectrophotometry and HPLC and a statistical analysis revealed that there were significant differences between HPLC and spectrophotometry. This study illustrates the importance of an official method for the dissolution test, since there is no official monograph for diltiazem hydrochloride in capsules.

Development and validation of a stability-indicating HPLC method for the determination of buclizine hydrochloride in tablets and oral suspension and its application to dissolution studies

A method using liquid chromatography has been developed and validated for determination of buclizine in pharmaceutical formulations and in release studies. Isocratic chromatography was performed on a C18 column with methanol:water (80:20 v/v, pH 2.6) as mobile phase, at a flow rate of 1.0 mL/min, and UV detection at 230 nm. The method was linear, accurate, precise, sensible and robust. The dissolution test was optimized and validated in terms of dissolution medium, apparatus agitation and rotation speed. The presented analytical and dissolution procedures can be conveniently adopted in the quality and stability control of buclizine in tablets and oral suspension.

Stability indicating HPLC method for simultaneous determination of moxifloxacin hydrochloride and ketorolac tromethamine in pharmaceutical formulations

A simple, RP-HPLC method was established for determining moxifloxacin and ketorolac in pharmaceutical formulations. Moxifloxacin, ketorolac and their degradation products were separated using C8 column with methanol and phosphate buffer pH 3.0 (55:45 v/v) as the mobile phase. Detection was performed at 243 nm using a diode array detector. The method was validated using ICH guidelines and was linear in the range 20-140 µg mL-1 for both analytes. Good separation of both the analytes and their degradation products was achieved using this method. The developed method can be applied successfully for the determination of moxifloxacin and ketorolac.

A study on the inhibition of mild steel corrosion in hydrochloric acid by pyridoxol hydrochloride

The inhibition of the corrosion of mild steel in 2M hydrochloric acid solutions by Pyridoxol hydrochloride (PXO) has been studied using weight loss and hydrogen evolution techniques. The inhibitor (PXO) exhibited highest inhibition efficiency of 71.93% at the highest inhibitor concentration of 1.0 x 10-2M investigated and a temperature of 303K from weight loss result. Also, inhibition was found to increase with increasing concentration of the inhibitor and decreasing temperature. A first order type of mechanism has been deduced from the kinetic treatment of the weight loss results and the process of inhibition attributed to physical adsorption. The results obtained from the two techniques show that pyridoxol hydrochloride could serve as an effective inhibitor of the corrosion of mild steel in HCl acid solution. The compound obeys the Langmuir adsorption isotherm equation.

Simple and sensitive spectrophotometric methods for the determination of acebutolol hydrochloride in bulk sample and pharmaceutical preparations

A direct, extraction-free spectrophotometric method has been developed for the determination of acebutolol hydrochloride (ABH) in pharmaceutical preparations. The method is based on ion-pair complex formation between the drug and two acidic dyes (sulphonaphthalein) namely bromocresol green (BCG) and bromothymol blue (BTB). Conformity to Beer's law enabled the assay of the drug in the range of 0.5-13.8 µg mL-1 with BCG and 1.8-15.9 µg mL-1 with BTB. Compared with a reference method, the results obtained were of equal accuracy and precision. In addition, these methods were also found to be specific for the analysis of acebutolol hydrochloride in the presence of excipients, which are co-formulated in the drug.

Titrimetric and spectrophotometric assay of bupropion hydrochloride in pharmaceuticals using mercury(II) nitrate

Two simple, rapid and accurate methods for the determination of bupropion hydrochloride (BUP) in pure and in pharmaceutical preparations are described. Both methods are based on the measurement of the chloride of its hydrochloride. In the titrimetric method, the chloride content of bupropion hydrochloride is determined by titrating with mercury(II)nitrate using diphenylcarbazone-bromophenol blue as indicator. Titrimetric method is applicable over a range 2-20 mg of BUP and the reaction stoichiometry is found to be 2:1 (BUP: Hg(NO3)2). The spectrophotometric method involves the addition of a measured excess of mercury(II) nitrate reagent in formate buffer to the drug, and after ensuring the reaction had gone to completion, the unreacted mercury(II) is treated with a fixed amount of diphenylcarbazone, and absorbance measured at 515 nm. The absorbance is found to decrease linearly with increasing concentration of BUP and the calibration curve is linear over 1.0-15.0 µg mL-1 BUP. The proposed methods were successfully applied to the determination of BUP in commercially available dosage forms with good accuracy and precision, and without detectable interference by excipients. The accuracy was further ascertained by placebo blank and synthetic mixture analyses and also by recovery experiments via standard-addition procedure.

New reagents for the spectrophotometric determination of ranitidine hydrochloride

A new spectrophotometric method is proposed for the assay of ranitidine hydrochloride (RNH) in bulk drug and in its dosage forms using ceric ammonium sulphate (CAS) and two dyes, malachite (MAG) green and crystal violet (CV) as reagents. The method involves the addition of a known excess of ceric ammonium sulphate to ranitidine hydrochloride in acid medium, followed by the determination of unreacted CAS by reacting with a fixed amount of malachite green or crystal violet and measuring the absorbance at 615 or 582 nm respectively against the reagent blank. The Beer's law is obeyed in the concentration range of 0.4-8.0 µg/ ml of ranitidine hydrochloride (RNH) for RNH-MAG system and 0.2-1.6µg/ml of ranitidine hydrochloride for RNH-CV system. The molar Absorptivity, Sandell's sensitivity for each system were calculated. The method has been successfully applied to the determination of ranitidine hydrochloride in pure and dosage forms.

Potentiometric and conductimetric studies of chemical equilibria for pyridoxine hydrochloride in aqueous solutions: simple experimental determination of pKa values and analytical applications to pharmaceutical analysis

The combination of two low-cost classical procedures based on titrimetric techniques is presented for the determination of pyridoxine hydrochloride in pharmaceuticals samples. Initially some experiments were carried out aiming to determine both pKa1 and pKa2 values, being those compared to values of literature and theoretical procedures. Commercial samples containing pyridoxine hydrochloride were electrochemically analysed by exploiting their acid-base and precipitation reactions. Potentiometric titrations accomplished the reaction between the ionizable hydrogens present in pyridoxine hydrochloride, being NaOH used as titrant; while the conductimetric method was based on the chemical precipitation between the chloride of pyridoxine hydrochloride molecule and Ag+ ions from de silver nitrate, changing the conductivity of the solution. Both methods were applied to the same commercial samples leading to concordant results when compared by statistical tests (95 and 98% confidence levels). Recoveries ranging from 99.0 to 108.1% were observed, showing no significant interference on the results.

Conductometric determination of propranolol hydrochloride in pharmaceuticals

In this paper the conductometric titration of propranolol hydrochloride in pharmaceutical formulations using silver nitrate as titrant is proposed. The method was based on the formation of an insoluble salt (AgCl(s)) between the chloride of propranolol hydrochloride molecule and Ag(I) ions of the titrant AgNO3. The effect of the PROP-AgNO3 concentrations and the interval of time between the successive additions of the titrant on the shape of the titration curve were studied. The obtained recoveries for four samples ranged from 96.8 to 105%. The proposed method was successfully applied in the determination of propranolol hydrochloride in several pharmaceutical formulations, with results in close agreement at a 95 % confidence level with those obtained using official spectrophotometric method.

Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.