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Biomedical subjects

Ioannis Niopas

Publications and source records attributed to Ioannis Niopas.

12 recordsLinked to original sources

Development and validation of a high performance liquid chromatographic method for the determination of oxcarbazepine and its main metabolites in human plasma and cerebrospinal fluid and its application to pharmacokinetic study.

An isocratic reversed-phase HPLC-UV procedure for the determination of oxcarbazepine and its main metabolites 10-hydroxy-10,11-dihydrocarbamazepine and 10,11-dihydroxy-trans-10,11-dihydrocarbamazepine in human plasma and cerebrospinal fluid has been developed and validated. After addition of bromazepam as internal standard, the analytes were isolated from plasma and cerebrospinal fluid by liquid-liquid extraction. Separation was achieved on a X-TERRA C18 column using a mobile phase composed of 20 mM KH(2)PO(4), acetonitrile, and n-octylamine (76:24:0.05, v/v/v) at 40 degrees C and detected at 237 nm. The described assay was validated in terms of linearity, accuracy, precision, recovery and lower limit of quantification according to the FDA validation guidelines. Calibration curves were linear with a coefficient of variation (r) greater than 0.998. Accuracy ranged from 92.3% to 106.0% and precision was between 2.3% and 8.2%. The method has been applied to plasma and cerebrospinal fluid samples obtained from patients treated with oxcarbazepine, both in monotherapy and adjunctive therapy.

Acetonitriles↗

No increased levels of the nicotine metabolite cotinine in smokers with schizophrenia.

The prevalence of smoking cigarettes has repeatedly been found to be greater in schizophrenia as compared with other psychiatric patients and the general population. Patients with schizophrenia have been found to engage in heavy smoking and consumption of higher doses of nicotine, probably by deeper inhalation of cigarettes. The aim of the current study was to assess nicotine exposure through smoking by measuring urinary cotinine, the major nicotine metabolite, in a group of smokers from Greece of smokers with schizophrenia and smokers from the general population. Participants were current smokers and belonged to one of two groups: 35 patients with schizophrenia and 48 healthy controls matched in age, education, and gender. The quantitative analysis of cotinine, the major metabolite of nicotine, in urine samples was performed by a modified high performance liquid chromatography (HPLC). Patients with schizophrenia who smoke presented a significantly larger time interval between last cigarette smoked and urine sample collection, as well as a significantly higher average number of cigarettes consumed daily than normal smokers. Urinary cotinine levels of patients with schizophrenia who smoke did not significantly differ from that of normal smokers when adjusted for average number of cigarettes per day and time interval between last cigarette smoked and urine collection. These results suggest that patients with schizophrenia did not present higher nicotine exposure through smoking compared with smokers from the community. The pharmacokinetic or pharmacodynamic properties of nicotine, as well as patient medications of the patients may explain our findings.

Adult↗

A validated solid-phase extraction HPLC method for the simultaneous determination of the citrus flavanone aglycones hesperetin and naringenin in urine.

A simple, specific, precise, accurate, and robust HPLC assay for the simultaneous analysis of hesperetin and naringenin in human urine was developed and validated. Urine samples were incubated with beta-glucuronidase/sulphatase and the analytes were isolated by solid-phase extraction using C18 cartridges and separated on a C8 reversed phase column using a mixture of methanol/water/acetic acid (40:58:2, v/v/v) at 45 degrees C. The method was found to be linear in the 50-1200 ng/ml concentration range for both hesperetin and naringenin (r > 0.999). The accuracy of the method was greater than 94.8%, while the intra- and inter-day precision for hesperetin was better than 4.9 and 8.2%, respectively and for naringenin was better than 5.3 and 7.8%, respectively. Recovery for hesperetin, naringenin and internal standard 7-ethoxycoumarin was greater than 70.9%. The method has been applied for the determination of hesperetin and naringenin in urine samples obtained from a male volunteer following a single 300 mg oral dose of each of the corresponding flavanone glycosides hesperidin and naringin. The intra- and inter-day reproducibility through enzyme hydrolysis was less than 3.9% for both total (free + conjugated) hesperetin and naringenin. Stability studies showed urine quality control samples to be stable for both hesperetin and naringenin through three freeze-thaw cycles and at room temperature for 24 h (error < or = 3.6%).

Calibration↗

Validated high-performance liquid chromatographic method utilizing solid-phase extraction for the simultaneous determination of naringenin and hesperetin in human plasma.

Naringenin and hesperetin, the aglycones of the flavanone glucosides naringin and hesperidin occur naturally in citrus fruits. They exert a variety of pharmacological effects such as antioxidant, blood lipid-lowering, anticarcinogenic and inhibit selected cytochrome P-450 enzymes resulting in drug interactions. A specific, sensitive, precise, and accurate solid-phase extraction high-performance liquid chromatographic (HPLC) assay for the simultaneous determination of naringenin and hesperetin in human plasma was developed and validated. After addition of 7-ethoxycoumarin as internal standard, plasma samples were incubated with beta-glucuronidase/sulphatase, and the analytes were isolated from plasma by solid-phase extraction using C(18) cartridges and separated on a C(8) reversed phase column with methanol/water/acetic acid (40:58:2, v/v/v) as the eluent at 45 degrees C. The method was linear in the 10-300 ng/ml concentration range for both naringenin and hesperetin (r>0.999). Recovery for naringenin, hesperetin and internal standard was greater than 76.7%. Intra- and inter-day precision for naringenin ranged from 1.4 to 4.2% and from 1.9 to 5.2%, respectively, and for hesperetin ranged from 1.3 to 4.1% and from 1.7 to 5.1%, respectively. Accuracy was better than 91.5 and 91.3% for naringenin and hesperetin, respectively.

Chromatography, High Pressure Liquid↗

A validated HPLC determination of the flavone aglycone diosmetin in human plasma.

Diosmetin, 3',5,7-trihydroxy-4'-methoxy flavone, is the aglycone of the flavonoid glycoside diosmin that occurs naturally in foods of plant origin. Diosmin exhibits antioxidant and anti-inflammatory activities, improves venous tone and it is used for the treatment of chronic venous insufficiency. Diosmin is hydrolyzed by enzymes of intestinal micro flora before absorption of its aglycone diosmetin. A specific, sensitive, precise, accurate and robust HPLC assay for the determination of diosmetin in human plasma was developed and validated. Diosmetin and the internal standard 7-ethoxycoumarin were isolated from plasma by liquid-liquid extraction and separated on a C8 reversed-phase column with methanol-water-acetic acid (55:43:2, v/v/v) as the mobile phase at 43 degrees C. Peaks were monitored at 344 nm. The method was linear in the 10-300 ng/mL concentration range (r > 0.999). Recovery for diosmetin and internal standard was greater than 89.7 and 86.8%, respectively. Intra-day and inter-day precision for diosmetin ranged from 1.6 to 4.6 and from 2.2 to 5.3%, respectively, and accuracy was better than 97.9%.

Chromatography, High Pressure Liquid↗

Smoking impact on CYP1A2 activity in a group of patients with schizophrenia.

The purpose of the present study was to assess the impact of smoking on the metabolism of psychotropic drugs in a group of patients with schizophrenia, by measuring CYP1A2 activity. This activity was assessed by the molar ratio (MR) of caffeine metabolites in urine [(AFMU+1U+1X)/17U] and saliva (17X/137X). Participants were 40 patients with schizophrenia: 30 current cigarette smokers and 10 nonsmokers. The two groups (smokers and nonsmokers) differed significantly in their ratio of men to women (83% men and 17% women were among smokers compared with 50% men and 50% women nonsmokers). No other group differences were found regarding age, level of education, PANSS, extrapyramidal symptoms, age of symptoms onset, antipsychotic doses (chloropromazine equivalents), and anticholinergic drug used. Smokers had significant higher MR in urine (P<0.001) as well as in saliva (P=0.001) than nonsmokers, suggesting a higher activity of CYP1A2 dependent on smoking. When gender was used as a covariate, the differences between the two groups remained significant for MR. Cigarette smoking may be a factor influencing the plasma levels of antipsychotics that metabolized through CYP1A2. Clinicians should weight the possibility that smoking and the subsequent modulation of antipsychotic metabolism may be the main reason of treatment resistance. Furthermore, any attempt to reduce or cease smoking in patients with schizophrenia necessitates close monitoring of drug doses, because untoward adverse effects may emerge.

Adult↗

Evaluation of the bioequivalence of two tablet formulations of enalapril/hydrochlorothiazide after single oral administration to healthy volunteers.

The pharmacokinetic parameters of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide (CAS 75847-73-3 and CAS 58-93-5, respectively; Penopril as test and another commercially available preparation as reference) were compared in an open-label randomized single oral dose two-period cross-over design to 24 healthy volunteers under fasting conditions. Plasma concentrations of enalaprilat (CAS 76420-72-9), the pharmacologically active metabolite of enalapril, and hydrochlorothiazide were determined by a validated GC/MS and HPLC assay, respectively. Serial blood samples were collected prior to each administration and at 19 timepoints within 36 h after dosing. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios for enalaprilat were 99.3% to 118.9% (point estimate: 108.7%) for AUC(0-infinity), 97.3% to 116.9% (point estimate: 106.7%) for AUC(0-t), and 92.5% to 113.0% (point estimate: 102.3%) for Cmax, and for hydrochlorothiazide 92.3% to 105.1% (point estimate: 98.5%) for AUC(0-infinity), 92.7% to 105.4% (point estimate: 98.9%) for AUC(0-t), and 97.6% to 115.3% (point estimate: 106.0%) for Cmax, within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference enalapril/hydrochlorothiazide formulations are bioequivalent for both the extent and the rate of absorption.

Adult↗

Simultaneous reversed-phase high-performance liquid chromatographic method for the determination of diosmin, hesperidin and naringin in different citrus fruit juices and pharmaceutical formulations.

Diosmin, hesperidin and naringin are flavonoid glycosides that occur naturally in citrus fruits. They exert a variety of pharmacological properties such as anti-inflammatory, antioxidant and free radical scavenging and antiulcer effects and also inhibit selected cytochrome P-450 enzymes resulting in drug interactions. A reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous determination of diosmin, hesperidin and naringin in different citrus fruit juices and pharmaceutical preparations. Diosmin, hesperidin, naringin and the internal standard rhoifolin were separated using tetrahydrofuran/water/acetic acid (21:77:2, v/v/v) as the mobile phase at 34 degrees C, using a C8 reversed-phase column. The method was linear in the 0.25-20.0 microg/ml concentration range for all three flavonoid glycosides (r>0.999). The method has been successfully applied to the determination of all three flavonoid glycosides in several samples of different citrus fruit juices sold in Greece and for the determination of diosmin and hesperidin in pharmaceutical preparations.

Antioxidants↗

Determination of nifedipine in human plasma by solid-phase extraction and high-performance liquid chromatography: validation and application to pharmacokinetic studies.

Nifedipine, a dihydropyridine calcium channel antagonist, is widely used in the treatment of hypertension and other cardiovascular disorders. A simple, rapid, sensitive, precise and accurate HPLC method, using solid-phase extraction, for the quantitation of nifedipine in human plasma was developed and validated. The calibration graphs were linear in the 5-400 ng/ml concentration range (r>0.999). Recovery for nifedipine was greater than 93.9% and for internal standard nitrendipine was 96.1%. Intra-day and inter-day precision ranged from 1.4 to 4.2 and 3.9 to 5.6%, respectively. Intra-day and inter-day accuracy was ranged from 94.5 to 98.0 and 93.1 to 98.0%, respectively. The method was not interfered with by other plasma components and was applied for the determination of nifedipine in pharmacokinetic study after single oral administration of 10 mg nifedipine to 18 healthy male subjects.

Adult↗

A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies.

Glibenclamide is a potent second generation oral sulfonylurea antidiabetic agent widely used for the treatment of type II diabetes melitus. A rapid, sensitive, precise, accurate and specific HPLC assay for the determination of glibenclamide in human plasma was developed and validated. After addition of flufenamic acid as internal standard, the analytes were isolated from human plasma by liquid-liquid extraction. The method was linear in the 10-400 ng/ml concentration range (r > 0.999). Recovery for glibenclamide was greater than 91.5% and for internal standard was 93.5%. Within-day and between-day precision, expressed as the relative standard deviation (RSD%), ranged from 1.4 to 5.9% and 5.8 to 6.6%, respectively. Assay accuracy was better than 93.4%. The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5 mg tablet of glibenclamide to 18 healthy volunteers.

Area Under Curve↗

Evaluation of the bioequivalence and pharmacokinetics of two tablet formulations of isosorbide-5-mononitrate after single oral administration in healthy volunteers.

The pharmacokinetic parameters of two oral formulations of 20 mg tablets of isosorbide-5-mononitrate (CAS 16051-77-7, Dilavenil as test and another commercially available preparation as reference) were compared in an open-label, randomized, single oral dose, two-period cross-over design in 20 healthy volunteers under fasting conditions. Plasma concentrations of isosorbide-5-mononitrate were measured by a validated gas chromatographic assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 101.2% to 108.5% (point estimate: 104.7%) for AUC0-variation of, 101.6% to 110.7% (point estimate: 106.2%) for AUC0-t, and 98.1% to 115.5% (point estimate: 106.1%) for Cmax, within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference isosorbide-5-mononitrate formulations are bioequivalent for both the extent and the rate of absorption.

Adult↗

Flavone aglycones in glandular hairs of Origanum x intercedens.

On the leaf surfaces of Origanum x intercedens numerous peltate glandular hairs producing essential oil occur. Although all glandular hairs have the same anatomical and developmental pattern, they differ in the appearance of the contents of the subcuticular space. Thus, in many hairs the subcuticular space is homogeneously filled with essential oil, whereas in others, within the mass of the oil numerous droplets constituting another phase exist. These droplets were tested for the presence of flavone aglycones. From the chloroform extract of glandular hairs, the free flavone aglycones thymusin(5,6,4'-trihydroxy-7,8-dimethoxyflavone), 5,6,4'-trihydroxy-7,3'-dimethoxyflavone, thymonin (5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone), cirsimaritin (5,4'-dihydroxy-6,7-dimethoxyflavone), and genkwanin (5,4'-dihydroxy-7-methoxyflavone) have been isolated and identified by spectral methods.

Journal Article↗