Khalil I. Al-Khamis

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.

High-performance liquid chromatographic determination of furosemide in plasma and urine and its use in bioavailability studies.

A sensitive, selective and efficient reversed-phase high-performance liquid chromatographic (HPLC) method is reported for the determination of furosemide in human plasma and urine. The method has a sensitivity limit of 5 ng/ml in plasma, with acceptable within- and between-day reproducibilities and good linearity (r2>0.99) over a concentration range from 0.05 to 2.00 microg/ml. The one-step extract of furosemide and the internal standard (warfarin) from acidified plasma or urine was eluted through a muBondapak C18 column with a mobile phase composed of 0.01 M potassium dihydrogenphosphate and acetonitrile (62:38, v/v) adjusted to pH 3.0. Within-day coefficients of variation (C.V.s) ranged from 1.08 to 8.63% for plasma and from 2.52 to 3.10% for urine, whereas between-day C.V.s ranged from 4.25 to 10.77% for plasma and from 5.15 to 6.81% for urine at three different concentrations. The minimum quantifiable concentration of furosemide was determined to be 5 ng/ml. The HPLC method described has the capability of rapid and reproducible measurement of low levels of furosemide in small amounts of plasma and urine. This method was utilized in bioavailability/pharmacokinetic studies for the routine monitoring of furosemide levels in adults, children and neonate patients.

Spectrophotometric Determination of Domperidone Using δA Method

Abstract A spectrophotometric method for the assay of domperidone tablets (Motilium(R)−10 mg) is described. The mean percentage found for the active ingredient per tablet was 100.61 ± 1.19. The drug exhibits maximum absorption at 282 nm in 0.5 N-sulphuric acid and at 294 nm in 0.5 N-sodium hydroxide due to keto-enol tautomerism. δA at 300 nm proved to be linearly related to the drug concentration in the range 5-30 μg ml−1 with a coefficient of variation 1.09%.

TRIACYLGLYCEROLS-PROFILING BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY: A TOOL FOR DETECTION OF PORK FAT (LARD) IN PROCESSED FOODS

Abstract A rapid high-performance liquid chromatographic procedure for separation of the triacylglycerols (TG) of animal fats using refractive index detection is described. A LiChrospher-100 RP-18 (5 μm) column was used for the TG-profiling of pork, beef, mutton, chicken and turkey fats. Detection of pork fat in processed foods and lard in fat-admixtures is also discussed. TG-separation and checking genuinity and adulteration was achieved isocratically in ∼ 15 min. by using CH3CN/CH2Cl2 (58:42, v/v) at ambient temperature.

Rapid Determination of Bupropion in Human Plasma by High Performance Liquid Chromatography

Abstract A high performance liquid chromatographic (HPLC) technique has been developed for the determination of bupropion hydrocloride (Bup) in human plasma, using a reversed-phase method, with UV detection at 250 nm. The internal standard 5-(P-methylphenyl)-5-phenylhydantoin (MPPH), was used as an aid to quantitation. The plasma was deprotemized with acetonitrile and the clear supernatant was directly injected in the chromatographic system. The lower limit of quantitation was 5.0 ng/ml using only 100 μl of plasma sample. Linear regression analysis for the calibration plots obtained on five different days over a two-week period for the the two ranges used (10–250 ng/ml and 250–2000 ng/ml) in plasma indicated excellent linearity and reproducibility. The mean recovery of spiked Bup in plasma samples over the concentrations studied was found 96.5 ± 3.14%. The method revealed that more than 30% of Bup was lost when the supernatant was stored at room temperature for 24 hrs.

High performance liquid chromatographic determination of ranitidine in human plasma

Abstract A rapid reversed phase HPLC method for determination of ranitidine in human plasma has been developed. The procedure involved extraction of the drug from alkalinized plasma spiked with the internal standard (procainamide) using 4% v/v isopropanol in ethylacetate. The extract was evaporated under nitrogen and the residue was reconstituted with methanol and injected onto U-Bondapak C18 column. The mobile phase is 8% v/v acetonitrile in 10 mM potassium phosphate buffer (pH 5.1); at a flow rate of 2.5 ml/min and UV detection at 330 nm. The efficiency of extraction was 90% with a detection limit of 20 ng/ml. The within-day coefficient of variations ranged from 4.09% to 5.81%, whereas those of between-day were from 7.5% to 9.51%.

Comparative Study of Saudi-Marketed Products and US Drug Labeling

Drug package inserts from ten nonsteroidal antiinflammatory drugs marketed in Saudi Arabia were compared with their corresponding US labels to determine possible differences in their information content. These variations were assessed with special regard to the number of words used and the type of the information provided. The study showed that inserts of Saudi-marketed products generally conveyed limited and incomplete information. Possible adverse reactions, drug-drug interactions, and date of revision often were not included, although this information was present on the corresponding US labels. Comparisons of the package inserts of the same product from various pharmaceutical companies show wide variations in the amount of information provided. Determining the minimal level of information that must be included by the manufacturer in the package insert and the establishment of firm international guidelines by the World Health Organization could effectively reduce such variations.

High-Performance Liquid Chromatographic Method for Determination of Glibenclamide in Human Plasma

Abstract An HPLC method for quantitative determination of glibenclamide in human plasma is described. The methodology is based on simple one step extraction of glibenclamide and diazepam (internal standard) from human plasma with dichloromethane. The drugs were eluted from a resolve 5 u spherical C18 column with a mobile phase consisting of 0.05 M ammonium dihydrogen phosphate:methanol (40:60%, v/v) adjusted to pH 4.0 with phosphoric acid. The drug and the internal standard were eluted at a flow rate of 1.2 ml per minute, and the optimum detector wavelength was 230 nm. The chromatography time was eleven minutes and the resolution between the drug and internal standard was excellent. Quantitation was achieved by the measurement of peak area ratios and the minimum detectable concentration was 5 ng/ml. The calibration curve of the assay was linear over the range of 10–400 ng/ml. The intraday coefficient of variation were ranged from 0.53% to 3.19%, whereas interday coefficient of variation were from 2.31% to...

Phenytoin‐bupropion interaction: effect on plasma phenytoin concentration in the rat

Abstract— The effect of coadministration of bupropion (50 mg kg−1, p.o.) on the disposition profile of phenytoin has been studied in the rat. Plasma phenytoin concentration was measured serially for 10 h by HPLC. Bupropion had little or no effect on the pharmacokinetic parameters of an acutely administered dose of phenytoin. Following multiple doses of phenytoin however (i.e. steady state) the coadministration of bupropion resulted in significant increases in the elimination half‐life (t 1/2), the area under the plasma concentration‐time curve (AUC) and the time to maximum plasma concentration (tmax). Allowing for the limitations of single dose studies, these results point to a possible pharmacokinetic interaction between bupropion and phenytoin—the clinical significance of which needs to be assessed.

Bioequivalence evaluation of norfloxacin 400 mg tablets (Uroxin and Noroxin) in healthy human volunteers.

A bioequivalence study of two oral formulations of 400 mg norfloxacin was carried out in 18 healthy volunteers according to a single dose, two‐sequence, cross‐over randomized design at College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital. The two formulations were: Uroxin® (Julphar, United Arab Emirates) as test and Noroxin® (Merck Sharpe & Dohme, BV, Netherlands). Both test and reference formulations were administered to each subject after an overnight fasting on 2 treatment days separated by 1 week wash‐out period. After dosing, serial blood samples were collected for a period of 24 h. Plasma harvested from blood, was analysed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC0–t, AUC0–∞, Cmax, Tmax, T1/2, and Kel were determined from plasma concentrations for both the formulations and found to be in good agreement with reported values. AUC0–t, AUC0–∞, and Cmax were tested for bioequivalence after log‐transformation of data. No significant difference was found based on ANOVA; 90% confidence interval for test/reference ratio of these parameters were found within a bioequivalence acceptance range of 80–125%. Based on these statistical inferences, it was concluded that Uroxin® is bioequivalent to Noroxin®. Copyright