Haider A. J. Al Lawati

Enhancement of on chip chemiluminescence signal intensity of tris(1,10-phenanthroline)-ruthenium(II) peroxydisulphate system for analysis of chlorpheniramine maleate in pharmaceutical formulations.

The effect of detection chip geometry on chemiluminescence (CL) signal intensity of tris(1,10-phenanthroline)-ruthenium(II) peroxydisulphate system for analysis of chlorpheniramine maleate (CPM) in pharmaceutical formulations was investigated. It was observed that the design of the detection chip is very crucial and can play an important role in enhancing the CL signal intensity in this system. The CL signal intensity was enhanced 250% when a teardrop micromixer chip was used, compared to the commonly used serpentine chip geometry. The study was conducted using a multi-chip device. In this device, chip 1 was used to prepare and pump the reagent mixture, whereas chip 3 was used for pumping the sample. The two chips were connected to the teardrop chip (2) via silica capillary where detection took place. Non-linear regression curve fitting of the calibration data revealed that the calibration curves are best described by third order polynomial equation with excellent correlation coefficients (R(2)=0.9998) for the concentration range 7.69 × 10(-8) to 5.12 ×1 0(-5)mol L(-1). A linear response is also observed over the range 7.69 × 10(-8) to 1.28 × 10(-5)mol L(-1) (R(2)=0.9996) and the detection limit was found to be 5.49 × 10(-8)mol L(-1). The device was successfully used for the analysis of CPM in tablets and a multi-component cough syrup. Results were reproducible with relative standard deviation (RSD) of 0.6-1.1%.

Flow-based analysis using microfluidics-chemiluminescence systems

This review will discuss various approaches and techniques in which analysis using microfluidics-chemiluminescence systems (MF-CL) has been reported. A variety of applications is examined, including environmental, pharmaceutical, biological, food and herbal analysis. Reported uses of CL reagents, sample introduction techniques, sample pretreatment methods, CL signal enhancement and detection systems are discussed. A hydrodynamic pumping system is predominately used for these applications. However, several reports are available in which electro-osmotic (EO) pumping has been implemented. Various sample pretreatment methods have been used, including liquid-liquid extraction, solid-phase extraction and molecularly imprinted polymers. A wide range of innovative techniques has been reported for CL signal enhancement. Most of these techniques are based on enhancement of the mixing process in the microfluidics channels, which leads to enhancement of the CL signal. However, other techniques are also reported, such as mirror reaction, liquid core waveguide, on-line pre-derivatization and the use of an opaque white chip with a thin transparent seal. Photodetectors are the most commonly used detectors; however, other detection systems have also been used, including integrated electrochemiluminescence (ECL) and organic photodiodes (OPDs).

Analysis of fexofenadine in pharmaceutical formulations using tris(1,10-phenanthroline)–ruthenium(II) peroxydisulphate chemiluminescence system in a multichip device

A simple, rapid and sensitive method has been developed for the analysis of fexofenadine (FEX) in pharmaceutical formulations, using a tris(1,10-phenanthroline)-ruthenium(II) [Ru(phen)(3)(2+)] peroxydisulphate chemiluminescence (CL) system in a multichip device. Various parameters that influence the CL signal intensity were optimized. These included pH, flow rates and concentration of reagents used. Under optimum conditions, a linear calibration curve in the range 0.05-5.0 µg/mL was obtained. The detection limit was found to be 0.001 µg/mL. The procedure was applied to the analysis of FEX in pharmaceutical products and was found to be free from interference from concomitants usually present in these preparations.

Analysis of phenylephrine hydrochloride in pharmaceutical formulations and biological fluids using (2,2′-bipyridyl)ruthenium(II)-peroxydisulphate chemiluminescence system in a two-chip microdevice

A two-chip microdevice has been developed for the analysis of phenylephrine hydrochloride (PEH) in pharmaceutical formulations and biological fluids using (2,2′-bipyridyl)ruthenium(II) (Ru(bipy)32+)-peroxydisulphate chemiluminescence (CL) system. It was observed that a pre-derivatization step is required to obtain an analytically useful CL signal. Using 0.5 mol L−1 formaldehyde solution as derivatization reagent, eighteen-time enhancement in the CL signal was observed. The derivatization reaction, photoreaction of (Ru(bipy)32+) with peroxydisulphate to produce (Ru(bipy)33+), reaction of (Ru(bipy)33+) with the derivatization product and detection of the produced CL signal were all carried out in this two-chip microdevice using minute quantity of reagents (27 μL per run). Various parameters that influence the derivatization reaction and the CL signal intensity were optimized. These include pH, flow rates and concentration of reagents used. A linear response was observed over the range 0.25 μg mL−1 to 15.0 μg mL−1 (R2 = 0.9999) with RSD values of 0.03% (n = 15) for 1 μg mL−1. The limit of detection (LOD) was found to be 0.027 μg mL−1 (S/N = 3). The developed method was successfully applied for the analysis of PEH in biological fluids and pharmaceutical formulations.

A novel microfluidic device for estimating the total phenolic/antioxidant level in honey samples using a formaldehyde/potassium permanganate chemiluminescence system

A microfluidic device has been investigated as a tool for the estimation of the total phenolic content/antioxidant level in honey using an acidic potassium permanganate chemiluminescence (KMnO4-CL) detection system. Selected phenolic antioxidants, including quercetin, catechin, gallic acid, caffeic acid and ferulic acid, produced analytically useful chemiluminescence signals, with detection limits ranging between 2.4 nmol L−1 for gallic acid and 34.0 nmol L−1 for o-coumaric acid. The parameters that affect the chemiluminescence intensities of each antioxidant were carefully optimized, including chip geometry, volume and area of the detection chip, pH, and concentrations of reagents used and flow rates. The effect of formaldehyde and other enhancers on CL signal intensity was extensively investigated. The method was applied to honey samples. Nine different honey samples exhibited total phenolic/antioxidant levels of 41.2 to 765.4 mg kg−1 with respect to gallic acid. The Folin–Ciocalteu (FC) assay results were well correlated with the chemiluminescence results. The method was found to be selective, rapid and sensitive when used to estimate the total phenolic/antioxidant level, producing good agreement with reported results for honey samples.

Towards an ideal method for analysis of lisinopril in pharmaceutical formulations using a tris(2,2′-bipyridyl)-ruthenium(II)-peroxydisulfate chemiluminescence system in a two chip device

A novel, rapid, selective and sensitive method has been developed for analysis of lisinopril (LIS) in pharmaceutical formulations using a tris(2,2′-bipyridyl)-ruthenium(II) (Ru(bipy)32+) peroxydisulfate chemiluminescence (CL) system in a two chip device. The parameters that influence the CL signal intensity were carefully optimized. These include pH, flow rates and concentration of reagents used. Under optimum conditions, a linear calibration curve between 0.25 and 50.0 μg mL−1 was obtained. About 180 samples were analyzed per hour while the detection limit was found to be 0.067 μg mL−1. The method was applied for analysis of LIS in pharmaceutical products and was found to be free from interferences of acid-induced degradation (AID) products and other ingredients usually present in these preparations.

A comprehensive evaluation of three microfluidic chemiluminescence methods for the determination of the total phenolic contents in fruit juices

Three recently reported microfluidic chemiluminescence (MF-CL) methods (based on reactions with acidic permanganate enhanced by formaldehyde (KMnO4-COH), acidic cerium (IV) and rhodamine B (Ce-RB), and acidic cerium (IV) and rhodamine 6G (Ce-R6G) enhanced by SDS) for the determination of the total phenolic content (TPC) in juices were critically evaluated in terms of their selectivity. The evaluation was carried out using 86 analytes, including 22 phenolic compounds (phenolic acids and polyphenols), 6 known non-phenolic antioxidants, 9 amino acids and a number of proteins, carbohydrates, nucleotide bases, inorganic salts and other compounds. Each method was sensitive toward phenolic compounds (PCs). However, the KMnO4-COH CL system showed a higher sensitivity toward phenolic acids and also responded to non-phenolic antioxidants. The other two systems showed higher sensitivity toward polyphenolic compounds than to phenolic acids and did not responded to all other compounds including non-phenolic antioxidants.

An enhanced cerium(IV)-rhodamine 6G chemiluminescence system using guest-host interactions in a lab-on-a-chip platform for estimating the total phenolic content in food samples.

Two chemiluminescence-microfluidic (CL-MF) systems, e.g., Ce(IV)-rhodamine B (RB) and Ce(IV)-rhodamine 6G (R6G), for the determination of the total phenolic content in teas and some sweeteners were evaluated. The results indicated that the Ce(IV)-R6G system was more sensitive in comparison to the Ce(IV)-RB CL system. Therefore, a simple (CL-MF) method based on the CL of Ce(IV)-R6G was developed, and the sensitivity, selectivity and stability of this system were evaluated. Selected phenolic compounds (PCs), such as quercetin (QRC), catechin (CAT), rutin (RUT), gallic acid (GA), caffeic acid (CA) and syringic acid (SA), produced analytically useful chemiluminescence signals with low detection limits ranging from 0.35 nmol L(-1) for QRC to 11.31 nmol L(-1) for SA. The mixing sequence and the chip design were crucial, as the sensitivity and reproducibility could be substantially affected by these two factors. In addition, the anionic surfactant (i.e., sodium dodecyl sulfate (SDS)) can significantly enhance the CL signal intensity by as much as 300% for the QRC solution. Spectroscopic studies indicated that the enhancement was due to a strong guest-host interaction between the cationic R6G molecules and the anionic amphiphilic environment. Other parameters that could affect the CL intensities of the PCs were carefully optimized. Finally, the method was successfully applied to tea and sweetener samples. Six different tea samples exhibited total phenolic/antioxidant levels from 7.32 to 13.5 g per 100g of sample with respect to GA. Four different sweetener samples were also analyzed and exhibited total phenolic/antioxidant levels from 500.9 to 3422.9 mg kg(-1) with respect to GA. The method was selective, rapid and sensitive when used to estimate the total phenolic/antioxidant level, and the results were in good agreement with those reported for honey and tea samples.

Microfluidic photoinduced chemical oxidation for Ru(bpy)3 3 + chemiluminescence — A comprehensive experimental comparison with on-chip direct chemical oxidation

For the first time, the analytical figures of merit in detection capabilities of the very less explored photoinduced chemical oxidation method for Ru(bpy)32+ CL has been investigated in detail using 32 structurally different analytes. It was carried out on-chip using peroxydisulphate and visible light and compared with well-known direct chemical oxidation approaches using Ce(IV). The analytes belong to various chemical classes such as tertiary amine, secondary amine, sulphonamide, betalactam, thiol and benzothiadiazine. Influence of detection environment on CL emission with respect to method of oxidation was evaluated by changing the buffers and pH. The photoinduced chemical oxidation exhibited more universal nature for Ru(bpy)32+ CL in detection towards selected analytes. No additional enhancers, reagents, or modification in instrumental configuration were required. Wide detectability and enhanced emission has been observed for analytes from all the chemical classes when photoinduced chemical oxidation was employed. Some of these analytes are reported for the first time under photoinduced chemical oxidation like compounds from sulphonamide, betalactam, thiol and benzothiadiazine class. On the other hand, many of the selected analytes including tertiary and secondary amines such as cetirizine, azithromycin fexofenadine and proline did not produced any analytically useful CL signal (S/N=3 or above for 1μgmL-1 analyte) under chemical oxidation. The most fascinating observations was in the detection limits; for example ofloxacin was 15 times more intense with a detection limit of 5.81×10-10M compared to most lowest ever reported 6×10-9M. Earlier, penicillamine was detected at 0.1μgmL-1 after derivatization using photoinduced chemical oxidation, but in this study, we improved it to 5.82ngmL-1 without any prior derivatization. The detection limits of many other analytes were also found to be improved by several orders of magnitude under photoinduced chemical oxidation.

Determination of Common Adulterants in Herbal Medicine and Food Samples using Core-shell Column Coupled to Tandem Mass Spectrometry

High-performance liquid chromatography coupled to tandem mass spectrometry was used to develop and validate a rapid method to qualitatively and quantitatively analyse 18 common adulterants in herbal medicine and food samples. Initially, the mobile phase composition was optimized in three different columns: core-shell, monolithic and standard 3.5-µm-particle-size columns. The results show that the core-shell column provides the best separation. Moreover, the tandem mass spectrometry was optimized. The linear range for all adulterants was 0.5-500 μg mL-1. Finally, the samples that were supplied by the Public Authority of Customer Protection, Ministry of Health, and those collected from the local market were analysed. The results indicate that 7 of 33 analysed samples contained adulterants. The adulterated samples mainly contain sildenafil, tadalafil or vardenafil. The concentrations of these three adulterants in the samples were 0.18-39 wt%. This study is the first report in the Sultanate of Oman about adulteration in herbal medicine and food samples. The results clearly raise some concern and require proper plan of action to increase public awareness about this serious issue.