Giancarlo Palumbo

Simultaneous determination of losartan and hydrochlorothiazide in tablets by high-performance liquid chromatography.

A method for the simultaneous determination of losartan potassium and hydrochlorothiazide in tablets is described. The procedure, based on the use of reversed-phase high-performance liquid chromatography, is linear in the concentration range 3.0-7.0 microg ml(-1) for losartan and 0.5-2.0 microg ml(-1) for hydrochlorothiazide, is simple and rapid and allows accurate and precise results. The limit of detection was 0.08 microg ml(-1) for losartan and 0.05 microg ml(-1) for hydrochlorothiazide.

Effects of maternal exposure to polychlorobiphenyls (PCBs) on F1 generation behavior in the rat

The effect of Fenclor 42 (PCB) exposure of female rats (Fischer 344 strain) was studied through assessment of the behavioral development of their F1 progeny. Female rats were exposed to PCB according to the following treatment schedule: (A) (5 days) 2 weeks prior to mating, (B) during gestation (Days 6-15 of pregnancy), (C) during lactation (Days 1-21 after delivery). Behavioral endpoints of motor reflexes, motor coordination, activity (preweaning behaviors), and learning (postweaning behavior) were evaluated for PCB ip dosages of 5-10 mg/kg/day for 5 days (preconception exposure), and PCB oral dosages of 2-4 mg/kg/day for 10 days (in utero exposure) and of 1-2 mg/kg/day for 20 days (during lactation exposure). Dosage-dependent differences in the evaluated behaviors were found in the offspring of the PCB-exposed females when compared to the offspring of corn-oil (vehicle)-exposed females. Significant differences in the development of cliff avoidance reflexive behavior, swimming ability, and open field activity were particularly evident. Furthermore the PCB exposure of female rats during gestation and lactation resulted in impaired acquisition of the active avoidance behavior while preconceptional PCB exposure significantly affected active avoidance performance as reflected in increased number of avoidance responses to reach criterion for extinction. These results show that Fenclor 42 does possess a significant risk to the offspring of exposed females, and further illustrate the sensitivity of progeny behavioral assessment in detecting suspected functional teratogenesis.

Pharmacokinetics of Mitomycin C in Pelvic Stopflow Infusion and Hypoxic Pelvic Perfusion with and without Hemofiltration: A Pilot Study of Patients with Recurrent Unresectable Rectal Cancer

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high‐dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Simultaneous determination of 5-aminosalicylic acid, acetyl-5-aminosalicylic acid and 2,5-dihydroxybenzoic acid in endoscopie intestinal biopsy samples in humans by high-performance liquid chromatography with electrochemical detection

A high-performance liquid chromatographic method for the simultaneous determination of 5-aminosalicylic acid (5-ASA), acetyl-5-aminosalicylic acid (Ac-5-ASA) and 2,5-dihydroxybenzoic acid (5-HSA) in human endoscopic intestinal biopsy with electrochemical detection has been developed and validated. A liquid-liquid extraction procedure was used to isolate these drugs from the biological material prior to analysis. The compounds were separated on an Erbasil S reversed-phase column using methanol-critic acid-sodium hydrogenphosphate-heptane-sulfonic acid-disodium ethylenediaminetetraacetate (pH 3) as mobile phase. The method was linear from 1.0 to 300 ng ml-1 for 5-ASA, from 10 to 1000 ng ml-1 for Ac-5ASA and from 0.1 to 10 ng m-1 for 5-HSA. The limit of detection for 5-ASA and for Ac-5-ASA was 1 ng ml-1 and that for 5-HSA was 0.1 ng ml-1. This procedure is suitable for pharmacological and clinical studies of 5-ASA.

Determination of Ofloxacin, A New Oxazine Derivative in Human Serum, Urine, and Bile by High-Performance Liquid Chromatography

Abstract A simple and precise high-performance liquid procedure has been developed for the determination of Ofloxacin (DL-8280), a new oxazine derivative in human serum, urine and bile using Norfloxacin as internal standard. The work-up procedure involves a chemical extraction step followed by isocratic chromatography on a anion-exchange analytical column, with ultraviolet detection. The run time for the assay was 11.5 minutes.

Determination of tenoxicam in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection

Abstract A sensitive, specific and rapid liquid chromatographic procedure to selectively monitor tenoxicam in human plasma was developed and validated. Plasma samples were acidified and extracted using solid-phase exctration column. The procedure was linear from 0.1 to 10 μ.g/ml with a detection limit of 0.05μg/ml. The coefficient of variation for the procedure is 6.2% and 2.0% for the range of concentrations examinated. This method is suitable for pharmacological, toxicological and pharmacokinetic studies of tenoxicam.

Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of recurrent melanoma

BACKGROUND The treatment of patients with advanced or recurrent pelvic melanoma, which are often associated with lesions in the lower limbs, is still unsatisfactory and controversial. A simplified hypoxic pelvic and limb perfusion has been recently recommended to provide therapeutic options for palliation and possibly cure. METHODS A nonrandomized and noncontrolled phase II experimental study was performed in 11 patients with symptomatic unresectable recurrent melanoma of the pelvis and limb. Patients were submitted to hypoxic pelvic and limb perfusion with 25 mg/m(2) of melphalan, 50 mg/m(2) of cisplatin, 300 mg/m(2) of dacarbazine, and 75 mg/m(2) of epirubicin by means of a simplified balloon occlusion technique. Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. Response rate was 82% (95% confidence interval, 58% to 100%). Median time to disease progression was 12 months (range 9 to 30 months). Three-year overall survival was 34%. CONCLUSIONS Hypoxic pelvic and limb perfusion is a safe and good palliative treatment for patients with unresectable recurrent melanoma. Further studies are necessary to to confirm these data and to establish if refinements can be made with acceptable toxicity.

Development of a method for the determination of vardenafil in human plasma by high performance liquid chromatography with UV detection

A simple high-performance liquid chromatographic (HPLC) method with photometric detection is described for the determination of vardenafil hydrochloride, a phosphodiesterase V inhibitor, in human plasma. Chromatographic separation of the analyte and internal standard was achieved on an analytical 250 x 4.6 mm i.d. reversed-phase Kromasil KR 100 C(18) (5 microm particle size) column using a mobile phase of acetonitrile-potassium dihydrogen phosphate (30:70 v/v). The run time was less than 15 min. Column eluate was monitored at 230 nm. The linearity over the concentration range of 10-1500 ng/mL for vardenafil was obtained and the limit of quantification (LOQ) was 10 ng/mL. The method has been applied to analysis of the vardenafil concentrations for application in pharmacokinetic studies.

Simultaneous determination of lomefloxacin, fenbufen and felbinac in human plasma using high performance liquid chromatography

SummaryA simple, specific, and sensitive high-performance liquid chromatography method has been developed for simultaneous determination of the lomefloxacin, febufen, and felbinac in human plasma. Plasma-spiked with internal standard, was vortex-mixed for 1 min with a mixture of dichloromethane-diethylether (80:20, v/v). The evaporated extract was dissolved in 0.02 M NaOH. The extracts were chromatographed on an Supelcosil LCSAX column (5 μm 250×4.6 mm I.D.) equipped with a guard column with a mibile phase composed of acetonitrile and phosphate buffer, with ultraviolet detection. Drugs were resolved at ambient temperature on a flow rate was 1.2 mL min−1, and monitoring was performed at 280 nm. The detection limits for lomefloxacin was 0.05 μg mL−1, 0.02 μg mL−1 for fenbufen and 0.03 μg mL−1 for felbinac. No interference from other commonly administered drugs or endogenous substances was observed. The method is fast since it involves two extraction steps followed by evaporation of organic solvent and chromatography of the residue. This method was found to be applicable to pharmacokinetic and pharmacodynamic studies of each drug after the concomitant administration of lomefloxacin and febufen.

Chronic atrophic gastritis and risk of N-nitroso compounds carcinogenesis.

ZusammenfassungDie chronisch atrophische Gastritis gilt als Präcancerose für ein Magencarcinom. Um die Korrelation zwischen fortgeschrittenen Schleimhautveränderungen und von Faktoren, die auf den Magensaft wirken und bei denen man einen Zusammenhang mit der durch Nitratverbindungen verursachten Carcinogenese vermutet, zu studieren, wurde eine sorgfältige Analyse biochemischer und mikrobiologischer Parameter wie pH, die Zählung aller Lebewesen im Mikromilieu (TVC), die Zählung aller Nitratreduktase-positiven Bakterien (NRPBC), Nitrit (NO2−) und Tiocyanat (SNC−)-Spiegel, an 56 Magensaftproben durchgeführt, die endoskopisch von nüchternen Patienten gewonnen wurden; 28 Patienten litten an chronisch atrophischer Gastritis (CAG), 14 hatten ein Magencarcinom (GC) und 14 dienten als Kontrollgruppe (NC). Die Mittelwerte von pH, Nitrit, TVC und NRPBC lagen in der Kontrollgruppe signifikant niedriger als in der Gruppe mit chronisch atrophischer Gastritis und Magencarcinomen. Weiter lagen die Mittelwerte einiger Parameter im Magensaft der Carcinompatienten höher als bei denen mit chronischer atrophischer Gastritis. Kein signifikanter Unterschied wurde zwischen den drei Gruppen für den Tiocyanatspiegel gefunden, der im wesentlichen durch Rauchergewohnheiten beeinflußt wurde. Die 28 Patienten mit chronisch atrophischer Gastritis wurden in zwei Gruppen unterteilt (Gruppe A: diffuse chronisch atrophische Gastritis — DCAG; Gruppe B: multizentrische chronisch atrophische Gastritis — MCAG) entsprechend dem Befall durch Schleimhautatrophie von Magencorpus und -fundus neben dem Antrum. Die Mittelwerte von pH, Nitrit, TVC und NRPBC waren in der MCAG-Gruppe signifikant höher als in der Kontrollgruppe, aber statistisch niedriger als in der DCAG- bzw. Carcinom-Gruppe. In diesen beiden Gruppen wurde kein Unterschied für die gleichen Variablen gefunden. Der Prozentsatz kontaminierten Magensaftes lag in der DCAG- und der Carcinom-Gruppe im Vergleich zur MCAG-Gruppe höher, kein Unterschied wurde zwischen DCAG- und Carcinom-Mägen gefunden. Das Ergebnis dieser Studie legt nahe, daß die diffuse chronisch atrophische Gastritis eher dem Risiko einer durch Nitratverbindungen verursachten Carcinogenese ausgesetzt ist.SummaryChronic atrophic gastritis is considered a precancerous condition for carcinoma of the stomach. To evaluate the correlation between progressive alterations in the mucosa and gastric juice microenvironmental factors, retained involved on N-nitroso compounds carcinogenesis, detailed analyses of biochemical and microbiological parameters such as pH, total viable counts (TVC), nitate reductase positive bacterial counts (NRPBC), nitrite (NO2−) and tiocyanate (SNC−) levels, were carried out on 56 fasting gastric juices samples obtained at endoscopy from 28 patients with chronic atrophic gastritis (CAG), 14 with gastric cancers (GC), and 14 normal controls (NC). The mean values of pH, nitrite, TVC, and NRPBC were significantly lower in the juices of NC than in those of CAG and GC patients. Furthermore, the mean levels of the same parameters were higher in GC than in CAG juices. No significant difference was found in the three groups for SCN− level which principally resulted influenced by smoke habit. The 28 patients with CAG were subdivided into two groups (Group A=Diffuse chronic atrophic gastritis — DCAG; Group B = Multifocal chronic atrophic gastritis —MCAG) according to the involvement of gastric corpus and fundus besides antrum by a process of mucosal atrophy. The mean levels of pH, nitrite, TVC, and NRPBC were significantly higher in MCAG than in normal controls but statistically lower in reference to DCAG and cancers. In these two groups no difference was found for the same variables. The percentage of contaminated juices was higher for DCAG and cancers in respect to MCAG but no difference was found between DCAG and neoplastic stomachs. The results of this study suggest that the DCAG could be considered as the chronic atrophic gastritis type more exposed to the risk of N-nitroso compounds carcinogenesis.