Automated stopped-flow system in pharmaceutical and clinical analysis : Kinetic determination of acetaminophen in formulations and serum by using the iron(II)—2,4,6-tris(2-pyridyl)-s-triazine

The development of automated stopped-flow spectrophotometric systems, their potential in automated routine determinations using kinetic and fast equilibrium techniques and several examples of applications are briefly reviewed. The use of a compact, inexpensive laboratory-made stopped-flow system for the measurement of reaction rates and a fast equilibrium method for the determination of acetaminophen in formulations and serum are described. The reaction-rate method is based on monitoring the oxidation of acetaminophen by iron(III) in the presence of the chelating agent 2,4,6-tris(2-pyridyl)-s-triazine to form a highly absorbing complex of iron(II). The calibration graph is linear in the range 20–200 μg ml^?1, with a precision of 0.8–2.6%, a detection limit of 5.5 μg ml^?1 and a measurement throughput of 120 per hour. Common excipients do not interfere and the analysis of commercial formulations gave results similar to those of a reference method. The optimization of the experimental conditions was done by a kinetic study of the reaction and some kinetic parameters are given.The method for the determination of acetaminophen in serum is based on a rapid measurement of the absorbance of the reaction mixture after a delay time of 15 s in the presence of chlorpromazine, which catalyses the reaction. Acetaminophen is isolated by extraction with ethyl acetate and the calibration graph is linear in the range 0.5–6 μg ml^?1 with a detection limit of 0.04 μg ml^?1 and a precision of 1.5%. The proposed method showed a decreased interference from drugs that also react with iron(III).     

Flow Injection Analysis of Famotidine with Spectrophotometric Detection

Abstract

A flow injection determination of famotidine has been described. The method is based on the reaction of the drug with cupric acetate to form a blue coloured complex which shows absorption maxima at 314 nm and 630 nm. For an injection volume of 100 μl calibration graphs were rectilinear from 10- 50 μg. ml^?1 and 50–500 μg.ml^?1 of drug at the two wavelengths respectively. Samples could be analysed at rates upto 60 per hour with a relative standard deviation less than 1.4%. The method was evaluated by analysis of the pure drug and commercial formulations. The results compare well with those obtained by official methods.     

Magnetic solid-phase extraction of rose bengal using iron oxide nanoparticles modified with cetyltrimethylammonium bromide

Magnetic solid phase extraction (MSPE) based on cetyltrimethylammonium bromide (CTAB)-coated magnetic iron oxide nanoparticles (C-MIONPs) was investigated for the separation, preconcentration and determination of Rose Bengal (RB) in aqueous solutions. The influences of different analytical parameters such as pH, temperature, ionic strength, volume of desorbent solvent, amount of adsorbent and interfering ions in the adsorption of RB on C-MIONPs were investigated. The RB adsorption on C-MIONPs follows Langmuir isotherm. The sizes of C-MIONPs were in the range of 20–80 nm. The method was capable of determining RB concentration in the range of 0.01–1.20 μg ml^?1. The limit of detection (LOD) of RB based on three times the standard deviation of the blank (3Sb) was found to be 5.91 × 10–3 μg ml^?1 (n = 8). The relative standard deviation (RSD) for 0.3 μg ml^?1 and 0.8 μg ml^?1 of RB were 4.1% and 1.1%, respectively. The proposed method was applied to the determination of RB in Brucella Antigen solution and water samples from the Karoon River.     

Colorimetric Determination of Propofol in Bulk form,Dosage Form and Biological Fluids

ABSTRACT

Propofol is coupled with 2, 6-dichloroquinone-4-chlorimide (DCQ) in a reaction buffered at pH 9.6 to give a colored product having an analytically useful maximum at 635 nm. The factors affecting the color generation were optimized and incorporated in the procedure. The reacted propofol has a molar absorptivity of 3.9 × 10^?4 L mol^?1 cm^?1, and Beer's law is obeyed for concentrations 1-5 μg ml^?1 with detection limit 0.25 μg ml^?1. The method was found applicable to biological fluids (plasma and urine) spiked with propofol at concentration levels 1-5 μg ml^?1 for plasma and 1-5 μg 0.5 ml^?1 urine (less sensitivity is obtained with urine volumes above 0.5 ml) with detection limits 0.28 μg ml^?1 for plasma and 0.4 μg 0.5 ml^?1 urine. The average recovery for the commercial preparation (1% w/v propofol emulsion intravenous injection for infusion) was 99.54% with an RSD of 1.05%. The method was validated by an adopted HPLC method. The results obtained by the HPLC method for the commercial preparation were statistically compared with the proposed method and evaluated at the 95% confidence limits.     

Phosphorescence detection in flowing systems: selective determination of aluminium by flow-injection liquid room-temperature phosphorimetry

The concept of the micelle stabilized liquid room-temperature phosphorescence (MS-LRTP) was applied to the determination of a metal (aluminium) in a flowing system. A three-line flow-injection manifold was developed and various parameters were optimized. A linear calibration graph was obtained for 0–4 μg ml^?1 aluminium. The limit of detection was 50 ng ml^?1 and the relative standard deviations for 0.1 and 1.0 μg ml^?1 aluminium were 2.7 and 1.3% respectively. The proposed procedure is fairly selective. More than 20 common ions studied did not interfere with the determination of aluminium or could be masked by appropriate reagents. The flow-injection method proposed was applied without any preliminary separation to the determination of aluminium in simulated synthetic samples in water and in clinical samples of particular importance in the control of aluminium toxicity in renal failure patients.     

Square‐Wave Adsorptive‐Stripping Voltammetric Detection in the Quality Control of Fluoxetine

ABSTRACT

A simple and sensitive extraction-spectrophotometric method for the determination of barium and potassium is reported. The 18C6-Barium-Orange II (18C6-Ba-(OR II)₂) and 18C6-Potassium-Orange II (18C6-K-OR II) ternary complexes are quantitatively extracted into dichloromethane and their absorbances are measured at 483 nm. Linear calibration graphs were obtained over the barium concentration range of 0.1-5 μg ml^?1 and potassium concentration range of 1-8 μg ml^?1. The relative standard deviation for 2.0 μg ml^?1 barium and pottasium are, respectively, 4.16% and 3.60%. The interfering effect of a large number of diverse ions on the determination of barium and potassium was studied. The method was applied to a synthetic sample with natural matrix effects of tap water and the results showed high potential of the recommended method for the determination of Ba and K in water samples.     

Simultaneous determination of Sb(III) and Sb(V) by partial least squares regression

A method for simultaneous spectrophotometric determination of Sb(III) and Sb(V) using multivariate calibration method is proposed. This method is based on the development of the reaction between the analytes and pyrogallol red at pH 2.00. The selection of variables was studied. A series of synthetic solutions containing different concentrations of Sb(III) and Sb(V) were used to check the prediction ability of the partial least squares model. The calibration curves were linear over the range of 0.3-3.4 and 0.3-3.0 μg ml⁻¹ for Sb(III) and Sb(V), respectively. The detection limits were 0.177 and 0.200 μg ml⁻¹ for Sb(III) and Sb(V), respectively.     

Differential pulse polarographic determination of traces of iron in solar-grade silicon

Iron is determined, after volatilization of the matrix as hexafluorosilicic acid, by means of the polarographic iron(III) wave in a 0.1 M triethanolamine—0.1 M potassium bromate—0.5 M sodium hydroxide medium. Differential pulse polarography provides a detection limit of about 0.15 μg g^-1 with a precision of 1–2% and linear calibration graphs up to 0.5 μg Fe(III) ml^-1.     

LC–QToF–MS method for quantification of ethambutol,isoniazid, pyrazinamide and rifampicin in human plasma and its application

In this research, we developed and validated a liquid chromatography coupled to mass spectrometry (LC–QToF–MS) method for simultaneous quantification of the anti-tuberculosis drugs ethambutol, isoniazid, pyrazinamide and rifampicin in human plasma. Plasma samples spiked with cimetidine (internal standard) were extracted using protein precipitation with acetonitrile containing 1% formic acid. Separation was performed using a C₁₈ column under flow gradient conditions with water and acetonitrile, both containing 5 mm ammonium formate and 0.1% formic acid. The method was validated according to the ANVISA and US Food and Drug Administration guidelines for bioanalytical method validation. The calibration curve was linear over a concentration range of 0.2–5 μg ml⁻¹ for ethambutol, 0.2–7.5 μg ml⁻¹ for isoniazid, 1–40 μg ml⁻¹ for pyrazinamide and 0.25–2 μg ml⁻¹ for rifampicin, all with adequate precision and accuracy. The method was reproducible, selective and free of carryover and matrix effects. The validated LC–QToF–MS method was successfully applied to real samples and shown to be applicable to future therapeutic and pharmacokinetic monitoring studies.     

The determination of hydrazine and 1,1-dimethylhydrazine,separately or in mixtures,by high-pressure liquid chromatography

A rapid, sensitive liquid chromatographic method for the determination of hydrazine and 1,1-dimethylhydrazine, separately or in mixtures of varying proportions, is described. The procedure involves salicylaldehyde derivative formation followed by chromatography on a reversed phase (octadecylsilane) column with acetonitrile (52%)—0.14 M potassium dihydrogenphosphate (48%) as a mobile phase and u.v. (254 nm) detection. This system is sensitive to 2 μg ml^-1 of hydrazine and 5 μg ml^-1 of 1,1-dimethylhydrazine and has a relative standard deviation of less than 1%. Monomethylhydrazine forms an unstable salicylaldehyde hydrazone; although it cannot be determined, it can be detected (sensitivity 5 μg ml^-1 ) and does not interfere with quantitative measurement of either hydrazine or 1,1-dimethylhydrazine.     

Flow Injection Analysis of Some Phenolic Sympathomimetic Drugs

ABSTRACT

A new, rapid and economical flow-injection (FI) method for deter-mining some phenolic sympathomimetic drugs is proposed. These drugs are etilefrine hydrochloride (ET), fenoterol hydrobromide (FT), hexoprenaline sulphate (HP), orciprenaline sulphate (OP) and reproterol hydrochloride (R.T). The determination is based on the reaction of the studied phenolic sympathomimetic drugs with 4-aminoantipyrine (4-AAP) and potassium hexacyanoferrate (III). The chemical reaction variables and also the FI variables, were optimized on the basis of sensitivity, sampling rate and reagent consumption. The proposed technique was applied to the analysis of pure raw materials in concentrations ranging from 2-20 μg.ml^?1 in case of ET, 4-30 μg.ml^?1 in case of FT and OP and from 8-50 μg.ml^?1 in case of HP and RT. Samples can be introduced at rates of about 130 per hour. The suggested procedure retained its accuracy and precision when applied to the analysis of pharmaceutical dosage forms containing the corresponding drugs, as judged by the RSD (%) and students' test. The results of the analysis were found to agree statistically with those obtained by applying either the official or the referee methods. Furthermore, the validity of the results was assessed by applying the standard addition technique.     

Cathodic stripping voltammetry of pipemidic acid and ofloxacin in pharmaceutical dosages and human urine

Sensitive cathodic stripping voltammetric methods have been developed for two quinolone antibacterial drugs, pipemidic acid (PIP) and ofloxacin (OFL) using hanging mercury drop electrode as working electrode vs. Ag/AgCl reference electrode. The methods were developed for the determination of drugs individually as well as simultaneously. 0.1 M and 0.01 M hydrochloric acid was used as medium for PIP and OFL, respectively, 0.1 M potassium chloride was used as base electrolyte. Reduction waves were observed for PIP within ?700 mV to ?800 mV and for OFL within ?1100 mV to ?1200 mV. Linear calibration ranges for PIP and OFL were observed within 10–100 μg ml^?1 with detection limits of 50 ng ml^?1 and 1 μg ml^?1, respectively. Relative standard deviations (RSD) for the analysis of 10 gµg ml^?1 of PIP and OFL (n = 6) were 0.5% and 1.4%, respectively. The presence of glucose, lactose, sorbitol, gum arabic, starch, magnesium stearate, methylparaben and propylparaben did not affect the determinations of both PIP and OFL. The methods were used for the analysis of pharmaceutical preparations and the results indicated relative deviation of 0.5–5.5% from labeled values with RSD within 0.49–2.5%. PIP and OFL could also be determined simultaneously, and were determined from spiked human urine.     

Analysis of Sarcandra glabra and its medicinal preparations by capillary electrophoresis

A simple, rapid, selective and reproducible capillary electrophoresis (CE) method was firstly developed for the identification and determination of isofraxidin and fumaric acid in a traditional Chinese herb Sarcandra glabra and its medicinal preparations. The buffer solution used in this method was 7.5 mM NaH₂PO₄ and 7.5 mM borax solution adjusted to pH 8.60. The linear calibration range was 1.25-800 μg ml⁻¹ (r=0.9997) for isofraxidin and 10-800 μg ml⁻¹ (r=0.9992) for fumaric acid, respectively. Under the optimum conditions, the relative standard deviation (R.S.D.) values of the migration time and the peak area were 0.47, 3.45% for isofraxidin and 0.83, 3.24% for fumaric acid, respectively. The recoveries ranged between 95.4-103.8% for isofraxidin and 97.1-104.7% for fumaric acid, respectively. The contents of isofraxidin and fumaric acid in Sarcandra glabra and two kinds of Sarcandra glabra-containing Chinese medicinal preparations were successfully determined within 8 min.     

Flow-injection determination of europium after on-line reduction

A zinc reductor minicolumn is used in a flow-injection system for reduction of europium(III) to europium(II). Europium(II) is indirectly determined either spectrophotometrically by oxidation with iron(III) and reaction of the iron(II) formed with 1,10- phenanthroline, or spectrofluorimetrically by reaction with cerium(IV) and measurement of the cerium(III) produced. The reductor functions efficiently at flow rates up to 1 ml min^?1, which allows sample injection rates up to 100 h^?1. Linear calibration is achieved for 10–200 and 0.5–4 μg ml^?1 with detection limits of 2.5 and 0.25 μg ml^?1, by spectrophotometry and spectrofluorimetry, respectively.     

Versatile automatic stopped-flow system for routine analysis

A versatile, automatic stopped-flow system featuring a mixing module and real-time data collection and treatment is presented. The mixing module is compatible with a number of spectrophotometers and spectrofluorimeters. The fast reaction between iron(III) and thiocyanate is used to evaluate the performance of the system and to develop a routine procedure for the determination of iron in wines, with a reaction time of 3 s. The calibration is linear over the range 1–30 μg ml^?1, with a r.s.d. of 0.9% (n = 11) for 10 μg Fe ml^?1 and a high sample throughput (120 h^?1) is achieved.     

Simultaneous kinetic determination of phosphate and silicate based on heteropoly blue formation

Small amounts of phosphate (0.08–1.16 μg ml^-1) and larger amounts of silicate (12–60 μg ml^-1) can be determined simultaneously by a kinetic method based on the difference in the rates of the heteropoly blue formation with molybdenum (V)—molybdenum (VI) mixtures in 0.28 M perchloric acid. The interference of large amounts of iron(III) on the determination of phosphate can be eliminated by masking with sodium hydrogen sulfite; this method is applicable to reagent-grade iron(III) chloride.     

Indirect determination of fluoride in waters with lanthanum alizarin complexone and inductively-coupled plasma emission spectrometry

Fluoride is determined indirectly by measurement of the La II 333.75-nm line in the lanthanum/alizarin complexone/fluoride complex. The ternary complex is extracted into hexanol containing N,N-diethylaniline and the extract is introduced directly into the plasma. Related to water samples, the detection limit (3σ, concentration factor 5) is 0.59 ng ml^?1 fluoride, calibration is linear up to 1.2 μg ml^?1 and the relative standard deviation for 0.04 μg ml^?1 is 2.6%. Alkali, alkali elements and most anions do not interfere. The method is applied in the analysis of river water, coastal seawater and drinking water.     

Spectrophotometric and Spectrofluorimetric Determination of Famotidine and Ranitidine Using 1,4-Benzoquinone Reagent

ABSTRACT

Spectrophotometric and spectrofluorimetric methods were adopted for the analysis of Famotidine and Ranitidine depending on their reaction with 1,4 Benzoquinone reagent at pH 5.2 and 5.6, respectively. The absorbances of the resulting condensation products were measured at 502 and 508 nm for Famotidine and Ranitidine, respectively. Concentrations adhering to Beer's law were from 40-160 μg.ml^? for Famotidine and from 20-100 μg.ml^? for Ranitidine.

Furthermore the resulting condensation products exhibited fluorescence at 665 nm when excited at 290 nm and the calibration graphs were rectilinear from 0.4-1.4 μg.ml^? for Famotidine and from 0.21 μg.ml^? for Ranitidine.

Different parameters affecting these reactions were thoroughly studied. Also these methods were applied to the pharmaceutical preparations and the results were satisfactory. The validities of the methods were ascertained by the standard addition technique revealing fine results in consideration to the mean recovery percent and standard deviation.

The spectrofluorimetric method was a hundred times more sensitive then the spectrophotometric method. The proposed methods were sensitive, accurate, and precise as statistically compared with the official methods of analysis of Famotidine and Ranitidine.     

Spectrophotometric Analysis of some Phenothiazine Neuroleptics using Chloramine-T

ABSTRACT

A sensitive and selective spectrophotometric method has been developed for the determination of six phenothiazine neuroleptics. The method is based on the interaction of the drugs with chloramine-T in sulphuric acid medium to yield a red, reddish-violet, orange or greenish-blue intermediate with maximum absorption at 500-636 nm. Beer's law is obeyed over the range 5-125 μg ml^?1 of the drugs. The apparent molar absorptivities were found to be in the range 1.04x10³ to 5.46x10³ 1.mol^?1cm^?1. The investigated drugs were assayed in tablets and injections. The mean percentage recoveries were 97.65-101.75 and the relative standard deviations were found to be less than 2%.     

Flow injection spectrophotometry followed by atomic Absorption spectrometry for the determination of iron(II) and total iron

In the flow system described, iron(II) is measured spectrophotometrically with 1,10-phenanthroline, and total iron is determined in the same flow line by atomic absorption spectrometry. Linear calibration ranges are 0.1–35 and 0.1–10 μg ml^?1 for iron(II) and total iron, respectively.