Badraddin M.H. Al-Hadiya

Liquid chromatographic assay of nifedipine in human plasma and its application to pharmacokinetic studies.

A highly sensitive, selective and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the determination of nifedipine in human plasma with minimum sample preparation. The method is sensitive to 3 ng/ml in plasma, with acceptable within- and between-day reproducibilities and linearity (r2 > 0.99) over a concentration range from 10-200 ng/ml. Acidified plasma samples were extracted using diethyether containing diazepam as internal standard and chromatographic separation was accomplished on C18 column using a mobile phase consisting of acetonitrile, methanol and water (35:17:48, v/v). The within-day precision ranged from 2.22 to 4.64% and accuracy ranged from 102.4-106.4%. The day-to-day precision ranged from 2.34-7.07% and accuracy from 95.1-100.1%. The relative recoveries of nifedipine from plasma ranged from 91.0-107.3% whereas extraction recoveries were 88.6-93.3%. Following eight 6-week freeze-thaw cycles, nifedipine in plasma samples proved to be stable with accuracy ranging from 0.64 to 3.0% and precision ranging from 3.6 to 4.15%. Nifedipine was also found to be photostable for at least 120 min in plasma, 30 min in blood and for 60 min in aqueous solutions after exposure to light. The method is sensitive and reliable for pharmacokinetic studies and therapeutic drug monitoring of nifedipine in humans after the oral administration of immediate-release capsules and sustained-release tablets to five healthy subjects.

Niclosamide: Comprehensive Profile

Publisher Summary This chapter presents a comprehensive profile of niclosamide, which is synthesized industrially by chlorinating salicylic acid in chlorobenzene to yield 5‐chlorosalicylic acid (I). Single‐crystal X‐ray structures of solvated forms of niclosamide revealed distinctly different modes of inclusion for different solvents. The X‐ray powder diffraction pattern of niclosamide is measured using a Philips PW-1050 diffractometer, equipped with a single‐channel analyzer and a copper K a radiation. Different methods of analysis are explained in the chapter. The electrochemical behavior of niclosamide is described on the basis of D.C. polarography, cyclic voltammetry, a.c. polarography, and differential pulse polarography, in the supported electrolytes of pH ranging from 2.0 to 12.0. Cyclic voltammetry, square‐wave voltammetry, and controlled potential electrolysis are used to study the electrochemical oxidation behavior of niclosamide at a glassy carbon electrode. The preparation of four niclosamide solvates and the study of their physical transformation and stability of the crystal forms in different suspension vehicles by differential scanning calorimetry (DSC) and thermal gravimetry (TG) are reported. Application of DSC and high performance liquid chromatography (HPLC) determine the effects of mixture composition and preparation during the evaluation of niclosamide‐excipients compatibility that showed that although some reactions occurred, niclosamide is compatible with a majority of common tablet excipients tested. Niclosamide inhibits oxidative phosphorylation and stimulates adenosine triphosphatese activity in the mitochondria of cestodes, killing the scolex and proximal segments of the tapeworm both in vitro and in vivo .

Validated liquid chromatographic-fluorescence method for the quantitation of gemifloxacin in human plasma

A highly selective, sensitive and rapid high performance liquid chromatographic method has been developed and validated to quantify gemifloxacin in human plasma. The gemifloxacin and internal standard (ciprofloxacin) were extracted by ultrafiltration technique followed by injection into chromatographic system. Chromatographic separation was achieved on a reversed phase C(18) column with a mobile phase of acetonitrile:0.1% trifluoroacetic acid (20:80, v/v) using isocratic elution (at flow rate 1 mL min(-1)). The analytes were detected at 269 and 393 nm for excitation and emission, respectively. The assay exhibited a linear range of 25-5000 ng mL(-1) for gemifloxacin in human plasma. The lower limit of detection was 10 ng mL(-1). The method was statistically validated for linearity, accuracy, precision and selectivity following FDA guidelines. The intra- and inter-assay coefficients of variation did not exceed 7.6% deviation of the nominal concentration. The recovery of gemifloxacin from plasma was greater than 97.0%. Stability of gemifloxacin in plasma was excellent with no evidence of degradation during sample processing (auto-sampler) and at least 3 months storage in a freezer at -70 °C. This validation method is applied for clinical study of the gemifloxacin in human volunteers.

PVC MATRIX MEMBRANE SENSORS FOR POTENTIOMETRIC DETERMINATION OF ARECOLINE

The construction and electrochemical response characteristics of Poly (vinyl chloride) (PVC) membrane sensors for arecoline HBr (AR) are described. The sensing membranes incorporate ion association complexes of (AR) cation and sodium tetraphenyl borate (NaTPB) (sensor 1) or phosphomolybdic acid (PMA) (sensor 2) or phosphotungstic acid (PTA) (sensor 3) as electroactive materials. The sensors display a fast, stable and near-Nernstian response over a relative wide AR concentration range (1 × 10−2 – 4 × 10−5 M) and (1 × 10−2 to 5 × 10−6 M), with cationic slopes of 52.5, 50.5 and 51.5 mV per concentration decade for sensor 1, 2, and 3, respectively over a pH range of 3.0–6.0. The sensors show good discrimination of AR from several inorganic and organic compounds. The direct determination of 1.5–2360.0 μg/ml of AR show an average recovery of 99.0, 98.5 and 99.5% and a mean relative standard deviation of 1.7, 1.6 and 1.5% at 200.0 μg/ml for sensor 1, 2 and 3 respectively. The proposed sensors have been applied for direct determination of AR in human saliva. The results obtained for determination of AR in saliva using the proposed method comparable favorably with those obtained using HPLC method.

Chapter 4 – Gemifloxacin

A comprehensive profile on Gemifloxacin, a novel fluoroquinolone synthetic broad-spectrum antibacterial agent for oral administration, particularly indicated for treatment of community-acquired respiratory tract infections, such as pneumonia and acute bacterial exacerbations of chronic bronchitis, is prepared. This profile contains the following sections: introduction, general physicochemical informations, X-ray powder diffraction patterns, methods of preparations, methods of analysis and stability, spectroscopic methods of investigations, and identifications including ultraviolet/visible spectroscopy, infrared (vibrational) spectroscopy, proton and carbon-13 nuclear magnetic resonance spectrometry, and mass spectrometry. Section 7 includes compendial BP identification methods, thin-layer chromatography, gas chromatography, high performance liquid chromatography. The pharmacological applications section includes uses, mode of action, pharmacokinetics, and toxicity investigations.

Co-administration of Fluoxetine Alters the Steady State Pharmacokinetics of Fluconazole after Multiple Oral Administration in Dogs

Objectives. Fluconazole is an antifungal agent which has become the mainstay treatment of opportunistic fungal infections in immuno-compromized patients. Fluoxetine is a selective serotonine reuptake inhibitor used in the treatment of psychiatric disorders. In the current study we investigated the effect of chronic administration of fluoxetine on the steady state pharmacokinetics parameters of fluconazole. Methods. The pharmacokinetics of Fluconazole, following 10 mg/kg single and multiple oral dosing for 10 days, was determined in dogs. Subsequently, the effect of 2 mg/kg fluoxetine given for 10 days, on the pharmacokinetics of Fluconazole was investigated. Results. The co-administration resulted in significant reduction of 40.1% and 35.6% in AUC  0- ∞ , and C max , respectively compared to fluconazole alone. A significant alteration of V ss / F was also seen as it increased from 0.242 ± 0.04 to 0.654 ± 0.17 l/kg ( P .01 ). Accordingly, a significant reduction in K el from 0.048 ± 0.01 hr-1 to 0.031 ± 0.01 was detected ( P .01 ). Conclusion. fluoxetine reduced plasma concentration of fluconazole. The mechanism of the interaction is probably the inhibition of OATP or other transporters in the intestinal wall. This interaction may have significant clinical importance because reduction in fluconazole may lead to treatment failure of fungal infection.

Chapter 5 - Parbendazole

Publisher Summary Benzimidazole derivatives act by interfering with metabolic pathways. Parbendazole has been shown to exhibit a broad-spectrum Anthelmintic activity. This compound is the most potent of a series of substituted 2-amino derivatives and is active against a wide variety of animal nematodes. The drug showed marked activity against third stage larvae that were located in the muscular tissue. It inhibits monoamine oxidase in animal nematodes. The drug was used with good effects against the common parasites of cattles, pigs, and horses. It acts quickly reaching peak blood levels 6-8h after administration. Its use in pregnant animals is contraindicated because of its teratogenicity; the defects are largely skeletal. Like other benzimidazoles, it suffers from the problem of resistance developing in the resident worm population if it is used persistently. The mode of action is not clearly delineated, but the following effects on the parasite, such as degeneration of microtubules, inhibition of glucose transport and uptake, interference with energy production, inhibition of fumarate reductase, ovicidal, cytoplasmic microtubules disappear in tegumentary and intestinal cells, secretory processes are discussed in this chapter. The toxicity of parbendazole in different doses was investigated with a group of animals. The side effects observed with the Anthelmintic were laxation (soft dung, diarrhea), anorexia, and listlessness.