Abdalla Shalaby

Monitoring phospholipids for assessment of ion enhancement and ion suppression in ESI and APCI LC/MS/MS for chlorpheniramine in human plasma and the importance of multiple source matrix effect evaluations.

Biological matrix effects are a source of significant errors in both electrospray (ESI) and atmospheric pressure chemical ionization (APCI) LC/MS. Glycerophosphocholines (GPChos) and 2-lyso-glycerophosphocholines (2-lyso GPChos) are known to fragment to form ions at m/z 184 and m/z 104, respectively. Phospholipids were used as markers to evaluate matrix effects resulting in both ion suppression and enhancement using ESI and APCI modes in the determination of chlorpheniramine in human plasma. Results revealed that GPChos and 2-lyso GPChos demonstrated very low ionization efficiency in the APCI mode, post-column infusion experiments were performed to confirm that suppression and enhancement matrix ionization effects coincided with the elution profiles of the phospholipids. The mean matrix effect for chlorpheniramine using APCI was 75% less than the mean matrix effect in ESI, making APCI the ionization method of choice initially even though the absolute response was lower than in the ESI mode. The resulting APCI method showed acceptable results according to the FDA guidelines; however, a multiple source relative matrix effects study demonstrated variability. It was concluded that an absolute matrix effects study in one source of biological fluid may be not sufficient to ensure the validity of the method in various sources of matrix. In order to obviate the multiple matrix source variability, we employed an isotopically labeled internal standard for quantification of chlorpheniramine in the ESI mode. An additional validation was completed with the use of chlorpheniramine-d(6) as the internal standard. This method met all acceptance criteria according to the FDA guidelines, and the relative matrix affects study was successful.

Spectrophotometric and AAS determination of ramipril and enalapril through ternary complex formation.

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of two antihypertensive agents (enalapril maleate and ramipril). The spectrophotometric procedures for the two cited drugs are based on ternary complex formation. The first ternary complex (copper(II), eosin, and enalapril) was estimated by two methods; the first depends on its extraction with chloroform measuring at 533.4 nm. Beers law was obeyed in concentration range from 56 to 112 microg ml(-1). The second method for the same complex depends on its direct measurement after addition of methylcellulose as surfactant at the pH value 5 at 558.8 nm. The concentration range is from 19 to 32 microg ml(-1). The second ternary complex (iron(III), thiocyanate, and ramipril) was extracted with methylene chloride, measuring at 436.6 nm, with a concentration range 60-132 microg ml(-1). The direct atomic absorption spectrometric method through the quantitative determination of copper or iron content of the complex was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and enalapril dosage forms.

Spectrophotometric and atomic absorption spectrometric determination of certain cephalosporins.

Two sensitive spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of certain cephalosporins (cefotaxime sodium and cefuroxime sodium). The spectrophotometric methods are based on the charge-transfer complex formation between these drugs as n-donors and 7,7,8,8-tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (p-CA) as pi-acceptors to give highly coloured complex species. The coloured products are measured spectrophotometrically at 838 and 529 nm for TCNQ and p-CA, respectively. Beers law is obeyed in a concentration range of 7.6-15.2 and 7.1-20.0 microg x ml(-1) with TCNQ, 95.0-427.5 and 89.0-400.5 microg x ml-1 with p-CA for cefotaxime sodium and cefuroxime sodium, respectively. The atomic absorption spectrometric methods are based on the reaction of the above cited drugs after their alkali-hydrolysis with silver nitrate or lead acetate in neutral aqueous medium. The formed precipitates are quantitatively determined directly or indirectly through the silver or lead content of the precipitate formed or the residual unreacted metal in the filtrate by atomic absorption spectroscopy. The optimum conditions for hydrolysis and precipitation have been carefully studied. Beers law is obeyed in a concentration range of 1.9-11.4 and 1.78-8.90 microg x ml(-1) with Ag(I), 14.2-57.0 and 13.3-53.4 microg x ml-1 with Pb(II) for cefotaxime sodium and cefuroxime sodium, respectively (for both direct and indirect procedures). The spectrophotometric and the atomic absorption spectrometric procedures hold well their accuracy and precision when applied to the analysis of cefotaxime sodium and cefuroxime sodium dosage forms.

Potentiometric determination of famotidine in pharmaceutical formulations.

Two new potentiometric methods for determination of famotidine in pure form and in its pharmaceutical tablet form are developed. In the first method, the construction of plasticised poly(vinyl chloride) (PVC) matrix-type famotidine ion-selective membrane electrode and its use in the potentiometric determination of famotidine in pharmaceutical preparations are described. It is based on the use of the ion-associate species, formed by famotidine cation and tetraphenyl borate (TPB) counterion. The electrode exhibited a linear response for 1 x 10(-3)-1 x 10(-5) M of famotidine solutions over the pH range 1-5 with an average recovery of 99.26% and mean standard deviation of 1.12%. Common organic and inorganic cations showed negligible interference. In the second method, the conditions for the oxidimetric titration of famotidine have been studied. The method depends on using lead(IV) acetate for oxidation of the thioether contained in famotidine. The titration takes place in presence of catalytic quantities of potassium bromide (KBr). Direct potentiometric determination of 1.75 x 10(-2) M famotidine solution showed an average recovery of 100.51% with a mean standard deviation of 1.26%. The two methods have been applied successfully to commercial tablet. The results obtained reveal good percentage recoveries, which are in good agreement with those obtained by the official methods.

HPLC Retention Index Scale for Nitrogen-Bridged Compounds

Abstract Retention indices of some nitrogen-bridged compounds having pharmacological activity have been determined. A retention index scale based on the relative retention of a homologous series of C3-C23 2-keto alkanes has been worked out. Linear relationships were found between RI and logP, allowing a prediction of retention indices. The relationships between the structures and the retention indices of these compounds have been interpreted.

Simple HPLC method for the analysis of some pharmaceuticals

Abstract A simple, selective, and accurate high performance liquid chromatographic method for the determination of cephalexine, cefotaxime, and salbutamol sulphate was developed. The suggested method uses ODS column with methanol-phosphate buffer (pH 7) 6:4 as a mobile phase. The mean percentage recovery ranged from 97.4 to 98.8. The proposed method was applied to the determination of the selected drug in some pharmaceutical preparations. The statistical analysis of the results obtained was compared favourably with those given with the official method.

Assessment of matrix effects and determination of niacin in human plasma using liquid–liquid extraction and liquid chromatography–tandem mass spectrometry

A simple, sensitive and rapid liquid-liquid extraction method for the analysis of nicotinic acid (niacin) and its labeled internal standard nicotinic acid-d4 (niacin-d4) in human plasma was developed and validated. The analyte and its internal standard were isolated from acidified plasma using a single liquid-liquid extraction procedure with methyl-t-butyl ether. The extracted samples were analyzed by liquid chromatography-tandem mass spectrometry in positive electrospray ionization mode with multiple reaction monitoring. The calibration curves were linear in the measured range between 5 and 1000 ng/mL and the limit of detection was calculated as 122 pg/mL. The method required 250 microL of human plasma and the total run time between injections was 3.5 min. Matrix effects were assessed by post-column infusion experiments, phospholipids monitoring and post-extraction addition experiments. The extraction of phospholipids and niacin from plasma was studied under acidic, neutral and basic conditions. Acidic conditions were optimal for both the recovery of niacin and the removal of phospholipids; the degree of matrix effects for niacin was determined to be 2.5%. It was concluded that effective removal of matrix components can overcome low recovery issues associated with liquid-liquid extractions of polar analytes.

Determination of ethambutol in pharmaceutical preparations by atomic absorption spectrometry, spectrophotometry and potentiometry

Simple methods are described for the determination of ethambutol in pharmaceutical preparations. They are based on the reaction of the drug with copper phosphate suspension in a borate buffer of pH 9.2, whereby a blue 1∶1 water-soluble copper-ethambutol complex is quantitatively formed. Four portions of the reaction solution are used for (i) measurement of copper by atomic-absorption spectrometry at 324.7 nm; (ii) potentiometric titration with EDTA with use of a solid-state copper ion-selective electrode; (iii) visual titration with EDTA (copper-PAN indicator); and (iv) spectrophotometric measurement of the copper-ethambutol complex at 640 nm. The results obtained are in good agreement and are better than those of the British Pharmacopoeia (BP) method.

Green Analytical Chemistry, Opportunities for Pharmaceutical Quality Control

This review article summarizes the opportunities for utilizing the green analytical chemistry (GAC) techniques and principles in the field of quality control (QC) of pharmaceuticals. Green analytical chemistry is considered a branch of the green chemistry based on the principles overlapping with the goals of sustainable development. General definitions of quality and quality control, the principles of GAC, proposals for greener sample pretreatment and greener chromatographic method of analysis applied in QC laboratories are discussed herein. The main goal is to achieve more eco-friendly analysis in QC laboratories through different strategies and techniques, replace toxic reagents, and modify or replace analytical methods and/or techniques with safer ones, making it possible to dramatically reduce the amounts of reagents consumed and waste generated.

Ion-Pair Chromatography of Nitrogen-Bridged Compounds on Silica Gel

Abstract New adsorption operations of high-performance ionpair chromatography have been investigated, using certain types of pharmacologically active nitrogen-bridged compounds. Various chromatographic data are reported. The effect of the counter ion concentration has been studied. Numerous examples of separations are presented.