Pharmacokinetic comparison of two 40 mg tablet formulations of citalopram using a new amperometric detection technique.

OBJECTIVES: To assess the bio-equivalence of two citalopram 40 mg tablet formulations (Lecital of the Jordan Sweden Medical and Sterilization Co. (JOSWE) as a test product, and Cipramil of Lundbeck (Denmark) as a reference product), and to develop a new high-performance liquid chromatography (HPLC) method using liquid-liquid extraction followed by addition of acid for the quantification of citalopram in human plasma. METHODS: A single-blind, randomized, single-dose, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a 20-day washout period in 24 healthy volunteers. The drug was administered with 240 ml of water after 10-h overnight fasting. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood was analyzed for citalopram by a novel method using HPLC coupled with an electrochemical detector. The limit of quantitation of citalopram was 1.493 ng/ml. Matrix-based calibration curves were linear over the range 1.493 - 80.640 ng/ml for citalopram. RESULTS: The average bioavailability and pharmacokinetic parameters of the two citalopram tablets were as follows: peak plasma concentration Cmax was 35.0 +/- 10.04 ng/ml and 33.4 +/-7.80 ng/ml for Lecital and Cipramil, respectively. The time to peak plasma concentrations tmax were 3.81 +/- 1.18 and 4.08 +/- 1.54 h, while the plasma half-life (t1/2) values were 54.0 +/- 7.50 and 54.7 +/- 10.6 h. The area under the plasma concentration-time profiles AUCo-t were 1,820 +/- 582 ng x h/ml and 1,660 +/- 510 ng x h/ml, whereas the AUC0-infinity were 2,010 +/- 663 ng x h/ml and 1,850 +/- 577 ng x h/ml for Lecital and Cipramil, respectively. The 90% confidence intervals for test/reference ratio were found within the acceptable limits of 80 - 125%, consequently no significant difference was found between the test and reference. CONCLUSION: Based on the pharmacokinetic and statistical results, it was concluded that Lecital 40 mg tablets of JOSWE is bioequivalent to Cipramil 40 mg tablets of Lundbeck (Denmark).

Simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma by high-performance liquid chromatography method using electrochemical detection with application to a pharmacokinetic study.

A method which employed high-performance liquid chromatography coupled with electrochemical detection was developed for the simultaneous determination of sildenafil and its metabolite, N-desmethyl sildenafil, in human plasma has. The method was developed and validated for purposes of its application to a pharmacokinetic study in healthy volunteers after an oral dose of 50mg/tablet under fasting conditions. High precision and accuracy were demonstrated. A one-step liquid-liquid extraction further provides a simple and practical way to process plasma samples containing sildenafil with good quantitative recovery. Sampling lasted for 24h after dosing; consequently a limit of quantitation (LOQ) of 7.858 ng/mL was achieved for sildenafil whereas a LOQ of 8.675 ng/mL was obtained for N-desmethyl sildenafil. The mobile phase consisted of acetonitrile, methanol and phosphate buffer (0.05 M) (18.5:34.5:47.0, v/v/v) pH 7.68. The stationary phase was a C(8) (150 mm x 4.6 mm), 5 microm particle size operated at 27 degrees C. All analytes were stable at the pH of the supernatant, and during the analytical time window. At the applied potential of +1.20 V versus Ag/AgCl, no interferences from endogenous plasma compounds were recorded at the retention times of sildenafil, N-desmethyl sildenafil. High resolution was obtained between the analytes and the employed internal standards.

Sorption of lead ions on diatomite and manganese oxides modified diatomite.

Naturally occurring diatomaceous earth (diatomite) has been tested as a potential sorbent for Pb(II) ions. The intrinsic exchange properties were further improved by modification with manganese oxides. Modified adsorbent (referred to as Mn-diatomite) showed a higher tendency for adsorbing lead ions from solution at pH 4. The high performance exhibited by Mn-diatomite was attributed to increased surface area and higher negative surface charge after modification. Scanning electron microscope pictures revealed a birnessite structure of manganese oxides, which was featured by a plate-like-crystal structure. Diatomite filtration quality was improved after modification by manganese oxides. Good filtration qualities combined with high exchange capacity emphasised the potential use of Mn-diatomite in filtration systems.

Bioequivalence evaluation of two brands of cefaclor 500 mg capsules: quantification of cefaclor using solid phase extraction technique.

OBJECTIVE: To assess the bioequivalence of two cefaclor 500 mg capsule formulations, and to develop a new high performance liquid chromatographic (HPLC) method using solid phase extraction technique for the quantification of cefaclor in human plasma. METHOD: An open, randomized, two-way, crossover trial with a one-week washout period in 25 healthy volunteers. The two commercial brands used were Recocef(Julphar, United Arab Emirates) as test and Ceclor(Eli Lilly, UK) as reference product. The drug was administered with 240 mL of water after a 10-h overnight fast. After dosing, serial blood samples were collected for a period of 8 h. Plasma harvested from blood was analysed for cefaclor by a new HPLC method using a solid phase extraction technique. The limit of detection of cefaclor was 17.6 ng/mL; average recovery was 96.5%; the intraday CV was less than 8% and interday CV was less than 13%. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2, and Kel, were determined from plasma concentrations for both formulations. Statistical analysis (ANOVA and 90% confidence intervals) were applied to AUC0-t, AUC0-infinity and Cmax for bioequivalence evaluation of two brands. The new HPLC method with solid phase extraction circumvented the problem of mixed polarity of cefaclor and facilitated its extraction from the complex plasma matrix while keeping the background free from interference due to endogenous plasma compounds. RESULTS: No significant difference was observed between the two brands of cefaclor capsules. CONCLUSION: Recocef was judged bioequivalent to Ceclor and the two products can therefore be considered to be interchangeable in medical practice.

Determination of mercury in biological fluids by potentiometric stripping analysis.

A method is described for the determination of mercury by potentiometric stripping analysis. The analyte, Hg(2+), is employed for oxidizing a fixed amount of cadmium, previously reduced and amalgamated at a thin mercury film preplated on a glassy carbon electrode. The cadmium stripping signal correlates well with the amount of Hg(2+) added. Correlation coefficients of 0.9971 and 0.9960 were obtained for the two working ranges: (25 ng-2.5 microg) and (5.0-50) microg Hg(2+), respectively, in spiked water samples. The method was investigated with respect to precision and accuracy by spiking a natural water sample with 25 microg Hg(2+).Nine replicate determinations gave a mean value of 24.8 microg with a standard deviation +/-0.31 microg. The 95% confidence limit of the mean suggested the absence of systematic errors. Using the highest possible sensitivity, detection limits of 2.0 ng (167 ng/l) and 0.5 ng (4.2 ng/100 ml of whole blood) were obtained in water and blood samples, respectively. The applicability of the method was successfully extended to include the more complex matrices after recording a zero blank from authentic samples spiked with Cd(2+) (25 microg).The described PSA procedure is a simple and rapid method compared with the cold-vapor technique, with a 5.2% and 4.9% RSD, respectively.

Disappearance of heme metabolites following chelation therapy with meso 2,3-dimercaptosuccinic acid (DMSA).

A lead poisoned adult (blood lead level 384 micrograms/dL) had a specific urinary porphyrin profile of elevated porphyrins including coproporphyrin III and 5-carboxylic acid derivatives. A multilinear gradient elution, modified with an ion-pair and a reversed phase column were employed for the separation of the diagnostically important porphyrin isomers. Fluorescence detection enhanced both sensitivity and selectivity. Both compounds were restored to normal levels following two courses of meso 2,3-dimercaptosuccinic acid: 90 mg/kg/d x 5 d at one month intervals. The decrease of clinical symptoms was associated with increase of delta aminolevulinic acid dehydratase from 53 to 230 U/mL blood and hemoglobin from 8.4 to 12.7 g/dL. Blood lead decreased from 384 to 24 micrograms/dL, urine lead from 1286 to 188 micrograms/L and urine coproporphyrin III from 5712 to 25 micrograms/L.