Y. M. El-Sayed

HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ANALYSIS OF CAFFEINE CONCENTRATIONS IN PLASMA AND SALIVA

A rapid high performance liquid chromatographic (HPLC) method for the analysis of caffeine in plasma and saliva is described. Samples of saliva and plasma were purified using zinc sulphate solution as protein precipitant. The supernatant was injected directly onto the column. The mobile phase consisted of ammonium acetate buffer:acetonitrile:methanol (82:15:3, v/v).

A RAPID HIGH‐PERFORMANCE LIQUID CHROMATOGRAPHY ASSAY OF GLIBENCLAMIDE IN SERUM

A rapid high‐performance liquid chromatography (HPLC) determination of glibenclamide in human serum is described. Serum samples to which flufenamic acid had been added as internal standard were treated with aceto‐nitrile as a protein precipitant. After centrifugation, separation and recon‐stitution, the redissolved residue was eluted from 5 μ Spherisorb C‐8 reversed phase column at ambient temperature using a mobile phase consisting of acetonitrile‐water (45: 55 v/v) at pH 3·7‐3·8 and pumped at a flow rate 2 ml/min. The effluent was monitored at 230 nm. The analysis time was no longer than 12min. A linear relationship between the peak height ratio (glibenclamide/flufenamic acid) and concentration was obtained in the range 20–400 ng/ml. A typical calibration curve has a regression equation y= 0·0035x + 0·015 (r = 0·9999). The detection limit of glibenclamide in serum was 20 ng/ml. The mean recovery of drug from serum samples spiked with known amounts of glibenclamide was 96·77%. Within‐day and between‐day coefficients of variation were 1·6‐4·0% and 1·4‐3·5%, respectively. Stability testing indicated that glibenclamide was stable for at least 10 days in serum — 20°C. The method developed was applied to determine some pharmacokinetic parameters after the oral administration of 5 mg glibenclamide tablets to a human volunteer.

IN VITRO AND IN VIVO EVALUATION OF SUSTAINED-RELEASE AND ENTERIC-COATED MICROCAPSULES OF DICLOFENAC SODIUM

AbstractThis work examines the release of diclofenac sodium from ethylcellulose (EC) microcapsules made up of different drug to polymer ratios. The release process was found to follow the Higuchi square root equation and not the zero-order or first order equations. However, for drug to polymer ratio of 1:1, a critical time (θ) was reached beyond which the release rate was lower than that predicted on the basis of the Higuchi square root equation. Dissolution experiments in 0.1N HCL revealed that less than 1.5% of the encapsulated drug was released in 6 h. This finding indicates the suitability of the EC microcapsules for enteric-coated preparations. The in vitro release of diclofenac sodium from microcapsules of different drug to polymer ratios was compared with that from a commercial sustained-release product. A distinct similarity between the release profile of the commercial product with that obtained for the 1:2 drug to polymer microcapsules was noted. The in vivo work included determination of the se...

A Stability-Indicating Hplc Analysis of Famotidine and Its Application to Kinetic Studies

Abstract A stability-indicating HPLC analytical method has been developed for the determination of the H2-receptor antagonist, famotidine in the presence of its degradation products. the method utilizes reversed phase chromatography with UV detection and internal calibration techniques. the mobile phase was comprised of 84% ammonium acetate buffer (pH 2.9) and 16% acetonitrile and pumped at a flow rate of 1.5 ml/min. Quantitation was performed by measuring the peak height ratio of drug to internal standard (salicylic acid). the limit of famotidine detection was determined to be 10 ng (0.4 ug/ml) with a signal to noise ratio of 3:1. Within day coefficient of variation of the method was 2.22% (2.5 μg/ml) and 0.82% (10 μg/ml). Between day coefficient of variation based on the slopes of daily prepared standard curves was 4.70%. the developed method was used to determine the drug content of famotidine tablets. Further, it was used to investigate the kinetics of degradation of the drug in an acidic solution.

The effect of oral activated charcoal on the systemic clearance of gentamicin in rabbits with acute renal failure.

Abstract— The effect of oral administration of activated charcoal on total body clearance of gentamicin administered intravenously (2 mg kg−1) has been studied in normal rabbits and rabbits with induced renal failure. Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits produced a significant reduction in gentamicin serum concentrations compared to control. Significant differences between treated and control groups, compatible with enhancement of gentamicin elimination, were observed in the calculated pharmacokinetic parameters (Kel, t 1/2, CL and AUC). To examine whether renal failure could augment the effect of activated charcoal in enhancing the systemic clearance of gentamicin, uranyl nitrate was used (0.75 mg kg−1, i.v.) to induce acute renal failure in rabbits. The derived pharmacokinetic parameters of gentamicin during the control phase in these animals were consistent with severe renal failure. The administration of activated charcoal, 2.5 h following gentamicin injection, produced a steeper decline in gentamicin concentration‐time profiles and significant changes in Kel, t 1/2 and CL. The Kel and CL values increased to about 200%, while the t 1/2 value decreased to about 50%. The apparent changes in the pharmacokinetic parameters induced by charcoal administration were more marked in rabbits with renal failure than in normal rabbits; however, induction of renal failure did not augment the charcoal‐induced clearance of gentamicin quantitatively.

Enhancement of Morphine Clearance Following Intravenous Administration by Oral Activated Charcoal in Rabbits

Abstract— A single dose of activated charcoal (10 g) significantly reduced the half‐life of elimination (1.02 ± 0.10 and 0.70 ± 0.04 h for the control and treated groups, respectively) and mean residence time (1.01 ± 0.12 and 0.76 ± 0.05 h for the control and treated groups, respectively) of morphine in rabbits. A 40% increase in the systemic clearance (85.73 ± 7.72 and 122.64 ± 16.32 mL min−1 kg−1 for the control and treated groups, respectively) and a 30% decrease in AUC (204.38 ± 22.20 and 140.03 ± 19.32 μg h L−1 in the control and treated groups, respectively) were also noted. Charcoal administration did not significantly alter the volume of distribution (Varea and VSS) or the apparent distribution half‐life. A two‐compartment model adequately described morphine kinetics in control and treated rabbits; charcoal administration produced a significant increase in the tissue compartment rate constant (K21). This finding indicates that activated charcoal not only enhances the systemic elimination of morphine, but also accelerates the rate of transfer of morphine from the tissue compartment to the central compartment.

BIOEQUIVALENCY OF RANITIDINE TABLETS

The bioavailability of two brands of ranitidine tablets was studied in 10 healthy volunteers. Formulation factors were compared by performing disintegration, dissolution and content uniformity tests. Plasma concentrations of ranitidine were measured using a sensitive and precise high pressure liquid chromatographic (HPLC) procedure. Pharmacokinetic parameters were determined for both formulations and included: Cmax, AUCt, AUCx, tmax, t1/2 and the terminal rate of elimination (k). Statistical analysis revealed that differences between the brands were not significant. The two formulations can be considered to be bioequivalent.

High performance liquid chromatographic analysis of cephalexin in serum and urine.

A rapid, highly sensitive high performance liquid chromatographic method has been developed for the determination of cephalexin in serum and urine. Serum protein was precipitated with 1% zinc sulphate solution containing cephradine as the internal standard.

Comparison of fluorescence polarization immunoassay and HPLC for the determination of theophylline in serum.

Theophylline in serum was measured by fluorescence polarization immunoassay (FPIA) and by high‐performance liquid chromatography (HPLC). Within‐run precision studies using control samples in the subtherapeutic, therapeutic and toxic concentrations, resulted in coefficients of variation in the range of 2·86–3·12% (FPIA) and 2·1–3·66% (HPLC), respectively. Between‐run precision ranged from 2·76‐6·2% for FPIA and from 2·51–6·0% for HPLC. The mean recovery for three spiked controls was 98·9% for FPIA and 98·8% for HPLC. Comparison of 60 patients samples, assayed with both methods, indicated an extremely good analytical correlation (r= 0·990). The FPIA method displayed a slight but consistent positive bias in relation to the concentration of theophylline present in patients sera. Caffeine was found to exhibit a positive bias to 13%, over a caffeine concentration range of 10–40 μg/ml. The HPLC method offers an advantage for measurements of both caffeine and theophylline simultaneously. The FPIA offers significant advantages in speed of analysis and turnover‐time, while maintaining accuracy and precision compared with those of established HPLC procedures.

PERFORMANCE OF TWO PREDICTIVE METHODS FOR CALCULATION OF THE KEY PHARMACOKINETIC PARAMETERS FOR GENTAMICIN DOSAGE INDIVIDUALIZATION

Performance of two methods for determination of the apparent volume of distribution (Vd) and the elimination half‐life (t1/2) for gentamicin was evaluated in 20 non‐obese acutely ill patients. The patients had varying degrees of renal function. Initial creatinine clearance ranged from 22·7–103·1 ml/min, with a mean value (± SEM) of 63·26 (±5·74) ml/min, and serum creatinine concentration was 1·37 (±0·13)mg/dl, witharange of 0·70‐3·0 mg/dl. The total daily dose of gentamicin ranged from 1·85‐4·71 mg/kg. Two different methods were used for Vd calculation: the Hull‐Sarubbi method and Chiou midpoint‐back‐extrapolation method. For t1/2 estimation, the Hull‐Sarubbi and Cutler methods were used. These values were compared with the values obtained by the Sawchuk‐Zaske method. Mean predicted error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were calculated for each method. Prediction bias and precision were compared statistically between each method by calculating the 95% confidence intervals of the δMA and δMAE, respectively. The MAEs revealed that the precision of Vd predictions were within 104 litre and 0·62 litre for the Hull‐Sarubbi and Chiou methods, respectively. For the elimination half‐life, none of the methods performance exhibited substantial bias. The Hull‐Sarubbi method, however, was less biased and more precise than the Cutler method.