Mohammed I. Al-hassan

Liquid chromatographic determination of six antiepileptic drugs and two metabolites in microsamples of human plasma.

A simple, rapid, sensitive, and reproducible high-performance liquid chromatographic (HPLC) method for simultaneous determination of the antiepileptic drugs (ethosuximide, primidone, lamotrigine, phenobarbital, phenytoin, and carbamazepine) and two metabolites (carbamazepine-diol and carbamazepine-epoxide) in human plasma is described. The procedure involves extraction of the drugs from human plasma (100 microL) with ether using 9-hydroxymethyl-10-carbamyl acridan as an internal standard. The extract was evaporated and reconstituted with mobile phase and then injected onto the chromatograph. The drugs and the internal standard were eluted from a Supelcosil LC-18 stainless steel column at ambient temperature with a mobile phase consisting of a 0.01M phosphate buffer/methanol/acetonitrile (65/18/17, v/v/v) adjusted to a pH of 7.5 with phosphoric acid and a flow rate of 1 mL/min. The effluent was monitored at 220 nm. Quantitation was achieved by using peak area ratio of each drug to the internal standard. The intraassay and interassay coefficients of variation (CV) ranged from 2.43% to 6.25% and from 3.02% to 5.85%, respectively. The absolute (extraction) and relative (analytical) recoveries for the drugs ranged from 70.7% to 104.4% and from 88.3% to 106.1%, respectively. Stability tests showed that the drugs were stable in plasma for at least 4 weeks when stored at -20 degrees C. The method was applied clinically for monitoring the AEDs in epileptic patients.

A rapid liquid chromatographic method for the determination of lamotrigine in plasma

A rapid sensitive and simple high-performance liquid chromatographic (HPLC) method for the determination of lamotrigine in plasma is described. The drug was extracted from 100 microliters of plasma with chloroform:isopropanol (95:5% v/v) in the presence of 100 microliters of phosphate buffer (10 mM). The extract was evaporated and the residue was reconstituted with mobile phase and injected onto the HPLC system. The drug and the internal standard (chloramphenicol) were eluted from a Symmetry C18 stainless steel column at ambient temperature with a mobile phase consisting of 0.01 M potassium-acetonitrile-methanol (70.20:10% v/v/v), adjusted to pH 6.7, at a flow rate of 1.3 ml min-1 and the detector was monitored at 214 nm. Quantitation was achieved by measurement of the peak-area ratio of the drug to the internal standard and the lower limit of detection for lamotrigine in plasma was 20 ng ml-1. The intraday precision ranged from 3.34 to 6.12% coefficient of variation (CV) and the interday precision ranged from 2.15 to 8.34% CV. The absolute and relative recoveries of lamotrigine ranged from 86.93 to 90.71% and from 95.18 to 107.13%, respectively. The method was applied in studying the pharmacokinetics of lamotrigine administered orally to rabbits. This reliable micro-method would have application in pharmacokinetic studies of lamotrigine where only small sample sizes are available, e.g. paediatric patients.

Halogenation of alkynes and alkynylsilanes

Abstract Halogenation of alkynes has given 1,2-dihalogenoalkenes in good yields. Bromination of alkylnylsilanes has given 1,2-dibromovinylsilanes, and reactions with iodine chloride mainly iodoalkynes.

Synthesis of cis- and trans-tamoxifen

Abstract The synthesis of cis-tamoxifen, non antiestrogenic tetrasubstituted olefin, was achieved via carboalumination of diphenylacetylene as a key step. Conversion to the antiestrogenic trans-tamoxifen was achieved by facile cis-trans isomerization of the corresponding phenol by acid or catalysts.

HYDROALUMINATION AND BROMINATION OF 1-(PHENYL-SELENYL)-1-ALKYNES

Hydroaluminuation and bromination of 1-(phenylselenyl)-1-alkynes were studied and compared with the rate of hydroalumination and bromination of the corresponding alkynylsilanes.

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.

Synthesis of mono- and diarylacetylenes

Abstract Arylacetylenes have been synthesized by CC coupling of lithium acetylide with aryl bromide in the presence of a palladium(0) catalyst.

Synthesis of Clomid Using Palladium-Catalyzed Cross-Coupling

Abstract Two methods of choice for the synthesis of clomid, a tetrasubstituted olefin with antiestrogenic activity, are described. The key reaction is hydroalumination of diphenylacetylene followed by C-C cross-coupling using catalytic amount of Pd0.

Synthesis of broparestrol using palladium-catalyzed cross-coupling

Abstract The synthesis of broparestrol, a biologically active tetrasubstituted olefin used in dermatology, was achieved via palladium-catalyzed cross-coupling to form a CC bond followed by bromination. Broparestrol (a cis-trans mixture of α-bromo-α,β-diphenyl-β-( p -ethylphenyl)ethylene) ( 1 ) is an estrogen, used in dermatology [1,2]. In this paper we report two advantageous methods of synthesizing broparestrol involving palladium-catalyzed cross-coupling.

Effects of Pregnancy on the Pharmacokinetics of Lamotrigine in Dogs

Summary: Purpose: This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG).