Revisiting flow‐chemiluminescence techniques: pharmaceutical analysis

The state of the art in flow‐chemiluminescence (flow‐CL) technique for automated pharmaceutical analysis is reviewed. Flow‐CL approaches have become powerful and promising tools for pharmaceutical screening in recent years due to their simplicity, low cost and high sensitivity. Because of these advantages, these methods have been widely used for pharmaceutical analysis in recent years. The literature reviewed covers papers of analytical interest that appeared between 2007 and mid‐2012 and have been divided into several sections based on fundamental types of CL systems employed. Furthermore, entries have been summarized alphabetically in tabular form giving details of analytical figures of merit of the methods. Copyright © 2012 John Wiley & Sons, Ltd.     

Rapid chemiluminometric determination of gabapentin in pharmaceutical formulations exploiting pulsed‐flow analysis

In this study, a straightforward and automated pulsed flow‐based procedure was developed for the chemiluminometric determination of gabapentin [1‐(aminomethyl)cyclo‐hexaneacetic acid], a new generation antiepileptic drug, in different formulated dosage forms. The software‐controlled time‐based injection method capitalizes on the decrease of the background chemiluminescence (CL) readout of the luminol–hypochlorite reaction in the presence of gabapentin. In short, gabapentin works as a hypochlorite scavenger. The analytical procedure was implemented in a multi‐pumping flow network furnished with a suite of microdispensing solenoid‐actuated pumps. The diaphragm‐type micropumps might be configured to operate as fluid propellers, commutation units and metering injectors. A dynamic linear working range for gabapentin concentrations in the range 60–350 µmol/L was obtained, with an estimated detection limit of 40 µmol/L. The flow analyser handles about 41 injections/h and yields precise results (RSD < 2%). The miniaturized flow analyser thus has potential to be exploited for in‐line monitoring of drug manufacturing within the quality assurance framework of modern pharmaceutical companies. Copyright © 2008 John Wiley & Sons, Ltd.     

CdS nanoparticles‐ enhanced chemiluminescence and determination of baicalin in pharmaceutical preparations

CdS nanoparticles (CdS NPs) of different sizes were synthesized by the citrate reduction method. It was found that CdS NPs could enhance the chemiluminescence (CL) of the luminol‐potassium ferricyanide system and baicalin could inhibit CdS NPs‐enhanced luminol‐potassium ferricyanide CL signals in alkaline solution. Based on this inhibition, a flow‐injection CL method was established for determination of baicalin in pharmaceutical preparations and human urine samples. Under optimized conditions, the linear range for determination of baicalin was 5.0 x 10^?6 to 1.0 x 10^?3 g/L. The detection limit at a signal‐to‐noise ratio of 3 was 1.7 x 10 ^?6 g/L. CL spectra, UV‐visible spectra and transmission electron microscopy (TEM) were used to investigate the CL mechanism. The method described is simple, selective and obviates the need of extensive sample pretreatment. Copyright © 2012 John Wiley & Sons, Ltd.     

DPPH·–luminol chemiluminescence system and its application in the determination of scutellarin in pharmaceutical injections and rat plasma with flow injection analysis

In this article, a DPPH·–luminol chemiluminescence (CL) system was reported and the CL mechanism was discussed according to the CL kinetic properties after sequence injecting DPPH· into the DPPH·–luminol reaction mixture. It was observed that scutellarin could inhibit the CL response of the DPPH·–luminol system. Based on this observation, a simple and rapid flow injection CL method was developed for the determination of scutellarin using the inhibition effect in alkaline medium. The optimized chemical conditions for the CL reaction were 5 × 10^?6 mol/L DPPH · and 1.0 × 10^?4 mol/L luminol in 0.01 mol/L NaOH. Under optimized conditions, the CL intensity was inversely proportional to the concentration of scutellarin over the ranges 5–2000 and 40–3200 ng/ml in pharmaceutical injection and rat plasma, respectively. The limits of detection (S/N  = 3) were 5 and 40 ng/ml in preparations and rat plasma, respectively. Furthermore, the precision, recovery and stability of the validated method were acceptable for the determination of scutellarin in both pharmaceutical injections and rat plasma. The presented method was successfully applied in the determination of scutellarin in pharmaceutical injections and real rat plasma samples.     

Rapid determination of isoamyl nitrite in pharmaceutical preparations by flow injection analysis with on‐line UV irradiation and luminol chemiluminescence detection

Isoamyl nitrite is used as a therapeutic reagent for cardiac angina and as an antidote for cyanide poisoning, but it is abused because of its euphoric properties. Therefore, a method to determine isoamyl nitrite is required in many fields, including pharmaceutical and forensic studies. In this study, a simple, rapid and sensitive method for the determination of isoamyl nitrite was developed using a flow injection analysis system equipped with a chemiluminescence detector and on‐line photoreactor. This method is based on on‐line ultraviolet irradiation of isoamyl nitrite and subsequent luminol chemiluminescence detection without the addition of an oxidant. A linear standard curve was obtained up to 1.0 μM of isoamyl nitrite with a detection limit (blank + 3SD) of 0.03 μM. The method was successfully applied to determine isoamyl nitrite content in pharmaceutical preparations. Copyright © 2013 John Wiley & Sons, Ltd.     

Development of a new procedure for the determination of captopril in pharmaceutical formulations employing chemiluminescence and a multicommuted flow analysis approach

This paper describes a new technique for the determination of captopril in pharmaceutical formulations, implemented by employing multicommuted flow analysis. The analytical procedure was based on the reaction between hypochlorite and captopril. The remaining hypochlorite oxidized luminol that generated electromagnetic radiation detected using a homemade luminometer. To the best of our knowledge, this is the first time that this reaction has been exploited for the determination of captopril in pharmaceutical products, offering a clean analytical procedure with minimal reagent usage. The effectiveness of the proposed procedure was confirmed by analyzing a set of pharmaceutical formulations. Application of the paired t‐test showed that there was no significant difference between the data sets at a 95% confidence level. The useful features of the new analytical procedure included a linear response for captopril concentrations in the range 20.0–150.0 µmol/L (r = 0.997), a limit of detection (3σ) of 2.0 µmol/L, a sample throughput of 164 determinations per hour, reagent consumption of 9 µg luminol and 42 µg hypochlorite per determination and generation of 0.63 mL of waste. A relative standard deviation of 1% (n = 6) for a standard solution containing 80 µmol/L captopril was also obtained. Copyright © 2015 John Wiley & Sons, Ltd.     

Flow injection chemiluminescence determination of captopril based on its enhancing effect on the luminol–ferricyanide/ferrocyanide reaction

A new flow injection chemiluminescence method is described for the determination of captopril. It is based on the enhancing effect of captopril on the chemiluminescence reaction of luminol with potassium ferricyanide in alkaline solution in the presence of potassium ferrocyanide. The method allows the determination of captopril over 0.1–40 µg/mL range, with a relative standard deviation (SD) of 1.0% for the determination of 0.5 µg/mL captopril solution in 11 repeated measurements. The method was satisfactorily applied to the determination of captopril in commercial captopril tablets. The possible reaction mechanism is also discussed briefly. Copyright © 2002 John Wiley & Sons, Ltd.     

Inhibition of the system luminol-H2O2-Fe(CN)63− chemiluminescence by the Mn(II) indirect determination of isoniazid in a pharmaceutical formulation

A flow injection procedure for the indirect chemiluminescent determination of isoniazid is proposed. The method is performed in a flow-injection manifold provided with a solid-phase reactor. The reactor was made from manganese dioxide physically entrapped by polymerization; the redox reaction isoniazid–manganese dioxide released Mn(II) which was monitored through its inhibitory effect on the reaction between luminol and hydrogen peroxide in presence of potassium hexacyanoferrate(III). The procedure resulted in a linear calibration graph over the range 5–15 mg/L of isoniazid with a sample throughput of 43 samples/h. The influence of foreign compounds was studied and the method was applied to determination of the drug in a pharmaceutical formulation. © 1998 John Wiley & Sons, Ltd.     

Flow‐injection chemiluminescence determination of melamine in urine and plasma

A novel flow‐injection chemiluminescence method for the determination of melamine in urine and plasma was developed. It was found that melamine can remarkably enhance chemiluminescence emission from the luminol–K₃Fe(CN)₆ system in an alkaline medium. Under the optimum conditions, chemiluminescence intensity had a good linear relationship with the concentration of melamine in the range 9.0 × 10^–9–7.0 × 10^–6 g/mL, with a correlation coefficient of 0.9992. The detection limit (3σ) was 3.5 ng/mL. The method has been applied to determine the concentration of melamine in samples using liquid–liquid extraction. Average recoveries of melamine were 102.6% in urine samples and 95.1% in plasma samples. The method provided a reproducible and stable approach for the sensitive detection of melamine in urine and plasma samples. Copyright © 2011 John Wiley & Sons, Ltd.     

Sensitive determination of 2‐methoxyestradiol in pharmaceutical preparations and serum samples using flow injection chemiluminescence

A rapid and sensitive flow injection chemiluminescence (FI–CL) method is described for the determination of 2‐methoxyestradiol (2ME) based on enhancement of the CL intensity from a potassium ferricyanide–calcein system in sodium hydroxide medium. The optimum conditions for the CL emission were investigated. Under optimized conditions, a linear calibration graph was obtained over the range 1.0 × 10^‐8 to 1.0 × 10^‐6 mol/L (r = 0.998) 2ME with a detection limit (3σ) of 5.4 × 10^‐9 mol/L. The relative standard deviation (RSD) for 5.0 × 10^‐7 mol/L 2ME was 1.7%. As a preliminary application, the proposed method was successfully applied to the determination of 2ME in injection solutions and serum samples. The possible CL mechanism was also proposed. Copyright © 2013 John Wiley & Sons, Ltd.     

Sensitive determination of epinephrine in pharmaceutical preparation by flow injection coupled with chemiluminescence detection and mechanism study

A novel, rapid and sensitive method was described for the determination of epinephrine (EP) using flow injection analysis coupled with chemiluminescence (CL) detection, which based on EP enhanced the weak CL emission of luminol–KIO₄ system in NaOH solution. Parameters affecting the CL intensity and reproducibility were optimized systematically. Under the optimized experiment conditions, the net CL intensity was proportional to the concentration of EP in the range of 5.0 × 10^?8 to 1.5 × 10^?6 mol/L with a detection limit of 1.9 × 10^?9 mol/L. The relative standard deviation (RSD) was found to be 0.7% for 13 replicate determinations of 3.0 × 10^?7 mol/L EP. The applicability of the proposed method was illustrated in the determination of EP in pharmaceutical preparation. The recoveries of EP at different levels in EP hydrochloride injection were between 95.4 and 104.7%. One assay procedure takes only 27 s, and the sampling rate was calculated about to be 130 samples/h. The possible mechanism of the enhanced CL intensity was studied by examining CL spectra and UV–vis spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

Flow‐injection chemiluminescence determination of haemoglobin in the blood

In this study, a sensitive and simple flow‐injection chemiluminescence (CL) method was developed for the quantitative analysis of haemoglobin. The method is based on the ability of haemoglobin to enhance the CL signal generated by a H₂O₂–K₄Fe(CN)₆–fluorescein alkaline system enhanced by CdTe quantum dots. Under the optimized conditions, haemoglobin can be detected in concentration range 7.35 × 10^–9–2.5 × 10^–6 mol/L, with a detection limit (3σ) of 1.8 × 10^–9 mol/L and a relative standard deviation (RSD; for 5 × 10^–7 mol/L haemoglobin) of 2.06% (n = 11). The present CL method was successfully applied for the determination of haemoglobin in three kinds of blood samples taken from an infant, an adult man, an adult woman and two reference samples. Compared with previous reports, the CL method described in this work is simple and rapid, with high sensitivity. Copyright © 2012 John Wiley & Sons, Ltd.     

Chemiluminometric determination of ascorbic acid in pharmaceutical formulations exploiting photo‐activation of GSH‐capped CdTe quantum dots

An automated multi‐pumping flow system is proposed for the chemiluminometric determination of ascorbic acid in pharmaceutical formulations, relying on the ability of semiconductor nanocrystals to generate short‐lived reactive species upon photo‐irradiation. A photo‐unit based on visible‐light‐emitting diodes is used to photo‐excite cadmium telluride (CdTe) quantum dots capped with glutathione, leading to the generation of radicals that react with luminol under alkaline conditions, yielding the chemiluminescence. Ascorbic acid acts as a radical scavenger, preventing the oxidation of luminol, thus ensuring a concentration‐dependent chemiluminescence quenching. After system optimization, a linear working range of 5.0 × 10^‐7 to 5.0 × 10^‐6 mol/L ascorbic acid (r = 0.9967, n = 5) was attained, with a detection limit of 3.05 × 10^‐7 mol/L and a sampling rate of 200/h. The flow system was applied to the analysis of pharmaceutical formulations and the results were in good agreement with those obtained by the reference titrimetric procedure (RD < ± 4.3%, n = 7). Copyright © 2014 John Wiley & Sons, Ltd.     

Flow injection–chemiluminescence determination of acyclovir

The chemiluminescence (CL) reaction of acyclovir (ACV)–potassium permanganate, with formaldehyde as an enhancer, was investigated by the flow‐injection system, and a new method is reported for the determination of ACV on the basis of the reaction. The method is rapid, effective and simple for the determination of acyclovir in the range 0.2–80 mg/L, with a limit of detection of 0.06 mg/L (3 S:N), a relative standard deviation (RSD) of 3.7% for the determination of 1.0 mg/L acyclovir solution in 11 repeated measurements. The method has been applied to the determination of acyclovir in pharmaceuticals, with satisfactory results. The possible reaction mechanism is also discussed briefly. Copyright © 2011 John Wiley & Sons, Ltd.     

Flow‐injection chemiluminescence and electrogenerated chemiluminescence determination of escitalopram oxalate in tablet form

Rapid, simple and highly sensitive flow‐injection (FI) chemiluminescence (CL) and flow‐injection electrogenerated chemiluminescence (ECL) methods were developed for the determination of escitalopram oxalate (ESC), a selective serotonin reuptake inhibitor used as an antidepressant drug. The CL method was based on the CL reaction of ESC with acidic cerium(IV) and tris(2,2'‐bipyridyl)ruthenium(II) (Ru). Various experimental parameters affecting CL intensity were carefully studied and optimised. The method enabled the determination of 0.001‐50 µg/mL of ESC in bulk form with a correlation coefficient r = 0.9999. The limit of detection (LOD) was 0.01 ng/mL (S/N = 3). The ECL method was based on the ECL reaction of Ru with the drug in an acidic medium, permitting the determination of ESC in the range of 0.00001‐70 µg/mL with r = 0.9999 and LOD of 1 x 10^‐4 ng/mL. The proposed methods were applied to the determination of ESC in commercial tablets. The results were compared statistically with those obtained from a published method using t‐ and F‐tests. Copyright © 2012 John Wiley & Sons, Ltd.     

Sensitive determination of gentiopicroside in medicine and bio‐fluids using luminol‐myoglobin chemiluminescence combined with flow injection technique

A novel chemiluminescence method for the determination of gentiopicroside is presented, which was based on the inhibitory effect of gentiopicroside on the chemiluminescence reaction between luminol and myoglobin in a flow‐injection system. The decrement of chemiluminescence intensity was linear with the logarithm of gentiopicroside concentration over the range from 10.0 pg mL^?1 to 500.0 ng mL^?1 (r² = 0.9992), with a detection limit of 3.0 pg mL^?1 (3σ). At a flow rate of 2.0 mL min^?1, a complete analytical process could be performed within 0.5 min, including sampling and washing, with a relative standard deviation of less than 3.0% (n = 5). The proposed procedure was applied successfully in the determination of gentiopicroside in pharmaceutical preparations, human urine and serum without any pretreatment procedure. The possible mechanism of the reaction was also discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Flow-injection chemiluminescence determination of catecholamines based on their enhancing effects on the luminol-potassium periodate system.

A rapid and sensitive chemiluminescence (CL) method using flow injection analysis is described for the determination of four catecholamines, dopamine, adrenaline, isoprenaline and noradrenaline, based on their greatly enhancing effects on the CL reaction of luminol-potassium periodate in basic solutions. The optimized chemical conditions for the chemiluminescence reaction were 1.0 x 10(-4) mol/L luminol and 1.0 x 10(-5) mol/L potassium periodate in 0.2 mol/L sodium hydroxide (NaOH). Under the optimized conditions, the calibration graphs relating the CL signal intensity (peak height) to the concentration of the analytes were curvilinear and they were suitable for determining dopamine, adrenaline, isoprenaline, and noradrenaline in the range 0.1-10 ng/mL, 0.1-100 ng/mL, 1-100 ng/mL and 5-50 ng/mL, respectively, with the relative standard deviations of 0.8-1.7%. The detection limits of the method are 0.02 ng/mL for dopamine, 0.01 ng/mL for adrenaline, 0.1 ng/mL for isoprenaline and 2.0 ng/mL for noradrenaline. The sampling frequency was calculated to be about 60/h. The selectivity of the method was good, because a series of common ions or excipients, such as K(+), Ba(2+), CO(3)(2-), NO(3)(-), SO(4)(2-), PO(4)(3-), sodium citrate, sodium bisulphite, oxidate dopamine, starch, lactose, carbamide and gelatin, could not produce interference when their concentrations were 1000-fold than those of dopamine. The present method was successfully applied to the determination of the four catecholamines in pharmaceutical injections.     

Transient formation of the oxo–iron(IV) porphyrin radical cation during the reaction of iron(III) tetrakis‐5,10,15,20‐(N‐methyl‐4‐pyridyl)porphyrin with hydrogen peroxide in aqueous solution

The reaction of iron(III) tetrakis‐5,10,15,20‐(N‐methyl‐4‐pyridyl)porphyrin (Fe(III)TMPyP) with hydrogen peroxide (H₂O₂) and the catalytic activity of the reaction intermediates on the luminescent peroxidation of luminol in aqueous solution were studied by using a double‐mixing stopped‐flow system. The observed luminescence intensities showed biphasic decay depending on the conditions. The initial flashlight decayed within <1 s followed by a sustained emission for more than 30 s. Computer deconvolution of the time‐resolved absorption spectra under the same conditions revealed that the initial flashlight appeared during the formation of the oxo–iron(IV) porphyrin, TMPyPFe(IV) = O, which is responsible for the sustained emission. The absorption spectra 0.0–0.5 s did not reproduce well by a simple combination of the two spectra of Fe(III)TMPyP and TMPyPFe(IV) = O, indicating that transient species was formed at the initial stage. Addition of uric acid (UA) caused a significant delay in the initiation of the luminol emission as well as in the formation of the TMPyPFe(IV) = O. Both of them were completely diminished in the presence of UA equimolar with H₂O₂, while mannitol had no effect at all. The delay of the light emission as well as the appearance of TMPyPFe(IV) = O was directly proportional to the [UA]₀ but other kinetic profiles were not changed significantly. Based on these observations and the kinetic analysis, we confirmed the involvement of the oxo–iron(IV) porphyrin radical cation, (TMPyP)^·+Fe(IV) = O, as an obligatory intermediate in the rate‐determining step of the overall reaction, Fe(III)TMPyP + H₂O₂ → TMPyPFe(IV) = O, with a rate constant of k = 4.3 × 10⁴/mol/L/s. The rate constants for the reaction between the (TMPyP)^·+Fe(IV) = O and luminol, and between the TMPyPFe(IV) = O and luminol were estimated to be 3.6 × 10⁶/mol/L/s and 1.31 × 10⁴/mol/L/s, respectively. Copyright © 2003 John Wiley & Sons, Ltd.     

Flow‐injection chemiluminescence method for the determination of chloramphenicol based on luminol–sodium periodate order‐transform second‐chemiluminescence reaction

A new chemiluminescence (CL) reaction was observed when chloramphenicol solution was injected into the mixture after the end of the reaction of alkaline luminol and sodium periodate or sodium periodate was injected into the reaction mixture of chloramphenicol and alkaline luminol. This reaction is described as an order‐transform second‐chemiluminescence (OTSCL) reaction. The OTSCL method combined with a flow‐injection technique was applied to the determination of chloramphenicol. The optimum conditions for the order‐transform second‐chemiluminescence emission were investigated. A mechanism for OTSCL has been proposed on the basis of the chemiluminescence kinetic characteristics, the UV‐visible spectra and the chemiluminescent spectra. Under optimal experimental conditions, the CL response is proportional to the concentration of chloramphenicol over the range 5.0 × 10^?7–5.0 × 10^?5 mol/L with a correlation coefficient of 0.9969 and a detection limit of 6.0 × 10^?8 mol/L (3σ). The relative standard deviation (RSD) for 11 repeated determinations of 5.0 × 10^?6 mol/L chloramphenicol is 1.7%. The method has been applied to the determination of chloramphenicol in pharmaceutical samples with satisfactory results. Copyright © 2011 John Wiley & Sons, Ltd.     

Development of a sensitive flow‐injection–chemiluminescence detection method for the determination of laevodopa

A simple chemiluminometric method using flow injection has been developed for the determination of laevodopa, based on its sensitizing effect on the weak chemiluminescence (CL) reaction between Na₂SO₃ and acidic KMnO₄. Under optimum experimental conditions, the CL intensity was linearly related to the concentration of laevodopa from 3.4 × 10^–8 to 2.4 × 10^–5 mol/L and the detection limit was 1.1 × 10^–8 mol/L (s:n = 3). The relative standard deviation (RSD) of the proposed method calculated from 20 replicate injection of 3 × 10^–7 mol/L laevodopa was 3.3%. The correlation coefficient was 0.997. The method was successfully applied to the determination of laevodopa in commercial pharmaceutical formulations and spiked urine samples. Copyright © 2008 John Wiley & Sons, Ltd.