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Covering the literature from 2011 until recently, this review highlights the analytical strategies that have been adopted for the extraction and analysis by high performance liquid chromatography comprising without or with derivatization of biogenic amines in real samples of food and beverages. The alternative ways of detection by tandem mass spectrometry, potential of multiple reaction monitoring and extracted ion chromatograms have been utilized when analyses performed without any derivatization. The reagents employed for derivatization differ widely in their structures, involve a variety of reaction mechanism, and allow detection by UV-absorption, fluorescence or mass spectrometry. The development of such a large number of reagents for a single class of analytes demonstrates the continued endeavours to overcome the implicit difficulties associated with low molar mass and polar analytes in complex sample matrices, and the inherent importance of the analysis of biogenic amines. The discussion presented will allow the alternative techniques to be adopted for particular biogenic amines samples, and have better control over selectivity and sensitivity of the method.

A novel and highly selective method has been developed for the determination of aromatic primary amines by their conversion to dithiocarbamates by reaction with carbon disulphide, and then to isothiocyanates, which are volatile, by heating in the presence of a heavy metal ion. Zinc(II) was selected owing to its low toxicity and optimum yield of isothiocyanates. The latter were sampled by headspace-solid phase microextraction (HS-SPME) on divinylbenzene-carboxen-polydimethylsiloxane fibre, 50/30 μm. The HS-SPME procedure was optimized to provide adequate limits of detection in the analysis of aromatic amines in their real samples by gas chromatography with mass spectrometry (GC–MS) or flame ionization detection (GC–FID). The method gave rectilinear calibration graph, correlation coefficient and limit of detection, respectively, over the range 0.08–100 μg L −1 , 0.9950–0.9990 and 25–240 ng L −1 in gas chromatography–mass spectrometry, and 0.01–10 mg L −1 , 0.9910–0.9991 and 0.8–3.0 μg L −1 in gas chromatography–flame ionization detection. At two different levels, 10 and 40 μg L −1 , the range of intra-day RSD was 3.7–8.5% (GC–MS) and 3.3–9.2% (GC–FID), respectively. The proposed method is simple and rapid, and has been applied to determine aromatic primary amines in the environmental waters, food samples of ice cream powder and soft drinks concentrate, and food colours. The intra-day RSD in the analysis of real samples by GC–MS was in the range 3.6–6.2%. The food/colour samples were found to contain elevated levels of aniline and 2-toluidine.

Liquid-phase microextraction (LPME) has been investigated for trace analysis in the present work in conjunction with fibre-optic-based micro-spectrophotometry which accommodates sample volume of 1 microL placed between the two ends of optical fibres. Methods have been evolved for the determination of (i) 1-100 microM and 0.5-20 microM of thiols by single drop microextraction (SDME) and LPME in 25 microL of the organic solvent, respectively, involving their reaction with the Ellman reagent and ion pair microextraction of thiolate ion formed; (ii) 70 microg to 7 mg L(-1) of chlorine/chlorine dioxide by headspace in-drop reaction with alternative reagents, viz., mixed phenylhydrazine-4-sulphonic acid and N-(1-naphthyl)ethylenediamine dihydrochloride, o-dianisidine, o-tolidine, and N,N-diethyl-p-phenylenediamine; (iii) 0.2-4 mg L(-1) of ammonia by reaction with 2,4-dinitro-1-fluorobenzene to give 2,4-dinitroaniline which was diazotized and coupled with 1-naphthylamine, the resulting dye was subjected to preconcentration by solid-phase extraction and LPME; and (iv) 25-750 microg L(-1) of iodide/total iodine by oxidation of iodide by 2-iodosobenzoate, microextraction of iodine in organic solvent, and re-extraction into aqueous starch-iodide reagent drop held in the organic phase. LPME using 25-30 microL of organic solvent was found to produce more sensitive results than SDME. The cuvetteless spectrophotometry as used in combination with sample handling techniques produced limits of detection of analytes which were better than obtained by previously reported spectrophotometry.

A simple and rapid method has been reported for the determination of carbonyl compounds involving sample preparation by headspace single drop microextraction using 1-butanol as extraction solvent containing 2,4-dinitrophenylhydrazine for hydrazone formation, and direct transfer of the drop into the injector for high-performance liquid chromatography with diode array detection. An angle-cut polytetrafluoroethylene sleeve, 3 mm × 0.5 mm, was fixed at the tip of the syringe needle and this allowed the use of 7 μL drop of solvent drop for extraction and derivatization. The procedure has been optimized with respect to suitable solvent for headspace drop formation, drop volume, concentration of reagent, sample temperature, reaction time, and headspace-to-sample volume ratio. The method has been validated when rectilinear relationship was obtained between the amount of analyte and peak area ratio of hydrazones in the range 0.01–15 mg L −1 , the correlation coefficient over 0.996–0.999, and the limit of detection in the range 1.7–24.1 μg L −1 . Spiked real samples have been analyzed with adequate accuracy, and application has been demonstrated of the method for analysis of carbonyl compounds formed as oxidation products.

Conversion of nitrate into a nitro-phenol derivative by reaction with 2-methylphenol or 2,6-dimethylphenol allowed at least 100-fold enrichment of the derivative on Lichrolut EN polymeric cartridge, and it is stable for up to 1 month on the cartridge. The derivative could be eluted with ammonia–methanol mixture. This reaction for nitrate determination has permitted a choice of final measurement by UV-Vis spectrophotometry, liquid chromatography or gas chromatography–mass spectrometry when the limits of detection were 10, 6 and 3 μg l −1 , respectively, and the calibration range 20 μg to 10 mg l −1 nitrate. The method has been validated by spiking natural water samples, when the recovery of nitrate was 98.5–108.4% (relative standard deviation 2.5–6.1%).

Interference by large chloride matrix and high acidity in the sample, which makes chromatographic determination of low (μg l−1) level of bromide difficult, can be avoided by pre-column reaction of bromide with 2-iodosobenzoic acid and 2,6-dimethylphenol or 2-tert-butyl-4-methylphenol to form within 1 min 4-bromo-2,6-dimethylphenol and 6-bromo-2-tert-butyl-4-methylphenol, respectively. The derivative was extracted into cyclohexane and injected into the GC. The aqueous sample could be subjected to clean-up using LiChrolut EN sorbent to remove organic matter before derivatization. The bromo derivative could be extracted from up to 250 ml of sample without any breakthrough. A rectilinear calibration graph was obtained for 0.02–100 μg l−1 bromide with a correlation coefficient of 0.9993 (10 calibration points) using 2-tert-butyl-4-methylphenol as reagent and the method has a limit of detection of 5 ng l−1 bromide. This method has also been applied to determine bromide in table salt and concentrated hydrochloric acid and to the spiked samples when the recovery was in the range 98–104% (R.S.D. 0.8–2.2%). The proposed method is simple and precise and high concentrations of ionic impurities including chloride, as found in sea water and table salt and acidity, as in concentrated hydrochloric acid, can be tolerated.

Low concentrations of phenols and amines in environmental waters and their low breakthrough volume during solid-phase extraction (SPE) hinder the detection of phenols and aromatic amines, whereas ammonia and aliphatic amines are not suitable for SPE. Pre-column derivatization to arylbenzoates and N-alkyl- or N-arylbenzamides and their GC-MS is proposed to separate and determine phenols and amines in aqueous samples in the range 0.1–100 μg l−1 with correlation coefficients in the range 0.9910–0.9992. The limit of detection ranged from 7 to 39 ng l−1 for most analytes (90 ng l−1 for 2,3,6-trichlorophenol and 20 μg l−1 for ammonia) when 80 ml of sample were preconcentrated, after derivatization, on a styrene–divinylbenzene copolymer sorbent. The developed method was applied to spiked drinking water, groundwater and river water samples, and was used to detect halo-phenols in paper mill effluents. The average recovery ranged from 96 to 110% with RSD of 4–12%. The described method is rapid and can be applied to control the water quality of environmental waters with respect to three important classes of organic pollutants and ammonia.

Hydrogen sulfide in water stabilized with or absorbed from air in an alkaline mixture of zinc acetate and EDTA was treated with 4-N,N-diethylaminoaniline and iron(III) in sulfuric acid medium and the absorbance of ethylene blue was measured at 670 nm after 5 min. The molar absorptivity was found to be 9.42 × 105 l mol−1 cm−1. The ethylene blue dye could be preconcentrated by solid-phase extraction on a CN sorbent and eluted by potassium bromide solution in water–methanol leading to an enrichment factor of at least 50. Coloured samples were subjected to clean-up by using Lichrolut EN and the colourless eluate was treated for colour development. Rectilinear calibration graphs were obtained over the range 10–800 μg l−1 sulfide (r = 0.9997) without solid-phase extraction, and 1–100 μg l−1 sulfide (r = 0.9989) after solid-phase extraction of the dye. The limits of detection were 5 μg l−1 and 0.2 μg l−1 sulfide without and after solid-phase extraction, respectively. The interference of up to 100 mg l−1 thiols, 50 mg l−1 sulfite and 10 mg l−1 thiosulfate could be avoided by their masking with N-ethylmaleimide. Up to 10 mg l−1 fluoride and 100 mg l−1 thiocyanate did not cause any interference. Interference of up to 100 mg l−1 fluoride was avoided by masking with zirconyl nitrate. The method has been validated by analysing spiked river water samples, when the average recovery was 99% (range 96–104%) with an RSD of 3% (range 2–4%). Sulfide has been detected in many river waters at low μg l−1 levels.

Pre-column conversion of ammonia and a number of aliphatic amines into phenylthiourea or its derivatives by reaction with phenyl isothiocyanate, followed by HPLC, has been used for their determination in environmental waters. Optimum conversion was found when the reaction was carried out in sodium hydrogencarbonate–carbonate medium at 40°C for 15 min. Well separated peaks were obtained on a C18 column with an acetonitrile–water gradient (1 ml min–1) of 30% acetonitrile for an initial 5 min which was increased linearly to 100% over 15 min and then maintained isocratic for 5 min, the acetonitrile ratio finally being returned to 30% in 5 min. The derivatized analytes were subjected to off-line solid phase extraction on C18 sorbent. A linear calibration graph was obtained for 0.01–10 mg l–1 analytes with a correlation coefficient of 0.9954 for ammonia and in the range 0.9982–0.9996 for amines. The limit of detection for ammonia was 0.2 µg l–1 and for amines in the range 0.3–0.6 µg l–1. The method was applied to tap, underground, river and aquarium waters, the recovery being in the range 97–106% (RSD 1.8–4.5%). Many of the samples were found to contain more than the permissible limit of ammonia. Phenyl isothiocyanate is stable for long periods in aqueous medium over wide ranges of pH and temperature, and the resulting phenylthioureas have adequate retention on C18 sorbent and strong UV absorption, making this reagent suitable for the determination of amines in water.

Oxidation of phenylhydrazine-4-sulfonic acid to the 4-diazobenzenesulfonic acid cation and its electrophilic coupling with N-(1-naphthyl)ethylenediamine dihydrochloride to give an azo dye is a new reaction scheme that is proposed for the spectrophotometric determination (545 nm) of chlorine in air and free and combined chlorine residuals in environmental waters. Masking of free chlorine with acetone permitted the determination of combined chlorine residuals in water. The maximum molar absorptivity was found to be 1.46 × 106 l mol–1 cm–1. A rectilinear calibration graph was obtained for 2.5–100 µg l–1 Cl. The azo dye could also be preconcentrated by solid-phase extraction on a C18 sorbent, leading to an enrichment factor of at least 40-fold. The limit of detection (without enrichment) was 0.2 µg l–1 Cl. Up to 50 µg l–1 bromate, 10 mg l–1 chlorate, 40 µg l–1 copper(II) and 100 µg l–1 iron(III) did not interfere. Chlorine dioxide was removed by bubbling the water sample with nitrogen. A comparison of the proposed method with the standard 4-N,N-diethylaminoaniline procedure was made and advantages of the present method are noted.

During the past fifteen years since its introduction, single-drop microextraction has witnessed incessant growth in the range of applications of samples preparation for trace organic and inorganic analysis. This was mainly due to the array of modes that are available to accomplish extraction in harmony with the nature of analytes, and to use the extract directly for analysis by diverse instrumental methods. Whilst engineering of novel sorbent materials has expanded the sample capabilities of rival method of solid-phase microextraction, the single-drop microextraction - irrespective of the mode of extraction - uses common equipment found in analytical laboratories sans any modification, and in a much economic way. The recent innovations made in the field, as highlighted in this review article in the backdrop of historical developments, are due to the freedom in operational conditions and practicability to exploit chemical principals for optimum extraction and sensitive determination of analytes. Literature published till July 2011 has been covered.

The solution obtained by oxidizing some of the ascorbic acid to dehydroascorbic acid by reaction with potassium iodate is used as a reagent for the reduction of paraquat to a blue radical cation in the flow-injection spectrophotometric determination of paraquat. A rectilinear calibration graph was obtained over the range 0.1–100 μg ml−1 paraquat, and the limit of detection was 20 ng ml−1 paraquat (signal-to-noise ratio = 3). This reagent has been found superior to ascorbic acid alone or sodium dithionite because of the lower limit of detection, wide linear range of determination, rapid and high stability.

Nitrite has been determined by reversed-phase high-performance liquid chromatography by its pre-column reaction with 2-aminobiphenyl to give a diazonium salt and with iodide to form 2-iodobiphenyl. Chromatographic analysis was done using a C18-column, a mobile phase of aceto-nitrile - 0.05M sulfuric acid, 60:40 (v/v), detection at 254 nm and using biphenyl as an internal standard. The pre-column derivatization required about 8 min and the chromatographic separation was complete in about 10 min. As low as 8 μg 1−1 of nitrite could be determined with a limit of detection of 2 μg 1−1 Application of the proposed method to river water and pharmaceutical tablets has been demonstrated.

A new reaction scheme for the determination of free residual chlorine in the presence of other chlorine species, viz. chlorite, chlorate, combined chlorine and chlorine dioxide, has been evaluated. It is based on the oxidation of 4-nitrophenylhydrazine by free chlorine to the 4-nitrophenyldiazo cation and its electrophilic coupling with N -(1-naphthyl)ethylenediamine dihydrochloride to give an azo dye which absorbs maximally at 532 nm. Flow-injection systems are proposed for the determination of 0.05–10 μg ml −1 free chlorine by the reagent-injection technique, and 1–40 μg ml −1 free chlorine by sample injection. The limits of detection of free chlorine and mean R.S.D. (range) were 0.03 μg ml −1 and 0.9% (0.6–1.2%), and 0.4 μg ml −1 and 0.6% (0.4–0.8%), respectively. Only chlorine dioxide interferes. The results were in good agreement with those obtained by flow-injection N , N -diethyl- p -phenylenediamine spectrophotometric and classical iodimetric titration methods. Since chloramines do not interfere in free chlorine determination, a method was developed for the determination of total chlorine (and hence of combined chlorine by difference after determination of free chlorine) utilizing a secondary reaction of both free and combined chlorine with bromide to yield bromine which then acts as oxidizing agent. The sample throughput was 110 h −1 in both methods.

A flow-injection method is described for the determination of acetaminophen (paracetamol) (linear range 0.8.100 gmg ml −1 based on its oxidation with 2-iodylbenzoate in acid medium to produce a yellow-orange compound, believed to be N -acetyl-1,4-benzoquinoneimine, which is monitored at 445 nm. The sample throughput is 360 h −1 . The precision (R.S.D) of determination was 0.5−2%. The method was applied to the determination of acetaminophen in drug formlations, and evaluated by analyzing spiked sample solutions, a mean recovery of 1006% (range 96.3−105.2%) being obtained. No interference was observed from the common exicipients of drugs and other active substances, e.g., dipyrone, acetylsalicylic acid, salicylamide and oxyphenbutzone. Te possible application of the proposed method in content uniformity test and drug dissolution studies is indicated. Comparison of the present method with a liquid chromatographic method for acetaminophen determination gave a mean difference of 1.2% (range 0.4−2.4%).

Matrix interference removal is an important step when large volumes of aqueous samples are required to be processed to detect trace levels of analytes. A combination of two sample extraction methods has been used in this work with the aim of cleanup and preconcentration of analytes. For first objective, mild but preferential sorption of a range of analytes has been performed with in-tube solid-phase microextraction (SPME) using polytetrafluoroethylene (PTFE) tubing, and for the second, the eluate from in-tube SPME was subjected to on-fibre SPME using DVB/Caboxen/PDMS (30/50 μm) fibre. Knitting of PTFE tubing created secondary flow pattern that enhanced radial diffusion and retention of organic analytes. Up to 2 mg L −1 of a broad range of substances that are not extracted by PTFE include nitrogen containing aromatic heterocyclic compounds, anilines, phenols and certain organophosphorus pesticides, thus providing a clean extract using this method of sample preparation. The proposed combination of in-tube and on-fibre SPME produced a rectilinear calibration graph over 0.03–150 μg L −1 of a range of analytes using 60 mL of aqueous sample. The overall recovery of analytes was in the range 27–78%. The detection limits were between 6.1 and 21.8 ng L −1 . The R.S.D. was in range 5.4–8.2% and 4.2–6.5% in the analysis of respectively 2 and 20 μg L −1 of analytes.

A simple, rapid and sensitive high performance thin layer chromatographic method was developed and validated for the estimation of lacidipine. The sample preparation involved protein precipitation followed by an efficient solid phase extraction on C18 cartridge. The analytes were isolated from 1 ml of urine and recovered by pure ethyl acetate solution. The method employed TLC aluminium plate precoated with silica gel 60F254 as the stationary phase. The solvent system employed consists of toulene–ethyl acetate [6.5:3.5v/v]. This system gave a dense and compact spot of the drug at R f value of 0.45. The linear regression data for the calibration plots showed good linear relationship ( r =0.999) over the concentration range 10–80 ng. Recovery studies were performed at two different levels. The recovery data reveals that the R.S.D. for intra-day and inter-day analysis at 10 ng was found to be 0.84 and 0.22%, respectively. The proposed method was found to be useful for the routine analysis of pharmaceuticals and pharmacokinetic studies in human urine samples.

A real-time determination of iodide is proposed which involves the oxidation of iodide with 2-iodosobenzoate in the presence of N,N-dimethylaniline. The reaction is completed within 1 min to yield 4-iodo-N,N-dimethylaniline, which is extracted in cyclohexane and determined by GC-MS. It was also possible to determine iodine by derivatization in the absence of 2-iodosobenzoate, and iodate by its reduction with ascorbic acid to iodide and subsequent derivatization. A rectilinear calibration graph was obtained for 0.02–50 μg l−1 iodide with a correlation coefficient of 0.9998. The limit of detection was 8 ng l−1 iodide. The method was applied to the determination of iodate in iodized table salt and free iodide and total iodine in sea-water, and to spiked samples when the recovery was in the range 96.8–104.3% (RSD 1.9–3.6%). A sample clean-up by solid-phase extraction with a LiChrolut EN cartridge is proposed.

Background correction has been shown to be an effective and indispensable modification in the spectrophotometric determination of ascorbic acid. The decomposition of ascorbic acid in pharmaceutical samples was carried out by incubation with sodium hydroxide to give products that were insensitive to ultraviolet light. The rapid oxidation in air of ascorbic acid, especially in dilute solutions, was avoided by the use of the flow injection principle for spectrophotometric determination and by employing a carrier stream of an anti-oxidizing nature consisting of 6 micrograms ml(-1) of 2-mercaptoethanol in 0.25% sulphuric acid. The optimized method with a single channel manifold made use of a carrier stream flow rate of 1.1 ml min(-1), an injection volume of 50 microl, a delay coil of 50 cm (0.5 mm i.d.) and detection at 245 nm. The throughput was at least 180 injections h(-1). The proposed flow injection method yielded results for the analysis of 0-20 micrograms ml(-1) of ascorbic acid that were 99-102% (relative standard deviation 0.6% or better) in agreement with those produced by comparable methods involving titration with iodine, chloranil or 2,6-dichlorophenolindophenol [4-(2,6-dichloro-4-hydroxyphenylimino)cyclohexa-2,5-dieno ne], and high-performance liquid chromatography. When the agreement was not good (as low as 14% with respect to the method being compared), this was traced to the presence of substances which are known to interfere in one or other of the methods of comparison.

Two methods are described for the determination of amodiaquine in pharmaceuticals. In the first method, amodiaquine was treated with periodate at pH 7.5-8.5 to yield a chromogen, which is believed to be a 1,4-benzoquinone imine derivative, and extracted into chloroform for spectrophotometric assay. The maximum molar absorptivity was found to be 2.17 x 10(3) l mol-1 cm-1 at 442 nm. Primaquine and chloroquine, if present also, do not interfere. The second method, which was used for the simultaneous determination of amodiaquine, primaquine and chloroquine, is based on high-performance liquid chromatography on an octadecylsilane column using a mobile phase of methanol-water (80 + 20) containing 0.5% anhydrous acetic acid and an over-all concentration of sodium dodecyl sulphate of 0.5 mM, with detection at 340 nm.

Thallium (III) sulfate in dilute sulfuric acid quantitatively oxidizes isoniazid to nitrogen and 4-pyrldine carboxylic acid. The test material is reacted with a measured excess of the reagent, the residual amount being back-titrated with ascorbic acid using o-dianisidine or p-ethoxychrysoidine as indicator. 4-Aminosalicylic acid, thiacetazone, thiamine hydrochloride, lactose and a number of other excipients do not Interfere with the analysis.

The detection of nitrobenzene is based on its partial reduction with zinc in slightly acidic medium to yield phenylhydroxylamine, acid-catalyzed rearrangement to form a mixture of 2- and 4-aminophenol, and formation of indophenol blue by 4-aminophenol on oxidative coupling with an alkaline phenol solution. The limit of detection is 0.1 μg ml −1 nitrobenzene in the test solution. A positive test is also given by 2- and 3-nitrotoluene but various other aromatics containing nitro groups do not interfere. The method was tested on wastewaters.

Aromatic primary amines are determined by injection into dilute hydrochloric acid carrier which merges sequentially with 4-N-methylaminophenol and dichromate. The purple-red color formed by oxidative coupling of amines with 4-N-methylaminophenol is measured at 530 nm. In contrast to the manual procedure, the flow-injection procedure avoided errors arising from the instability of the coupling intermediate, oxidation of the amine, and too great an excess of the oxidant. The method improves the selectivity for certain amines in the presence of those which are sterically hindered or have an electron-deficient aromatic nucleus. Nitrite is determined by diazotization of sulfanilamide and quantifying the residual sulfanilamide by oxidative coupling. The sample thourghout for the assay of amines (0.05–20 μg ml−1 NH2-N) and nitrite (1–10 μg ml−1 NO2--N) was 120 h−1. A system for the consecutive determination of aromatic primary amines and nitrite is decribed.

Nitrite is determined by its reaction with a measured but excessive amount of pyridine-4-carboxylic acid hydrazide in acid medium (when the two substances react in a 1:1 molar ratio) and evaluation of the surplus hydrazide by titration with chloramine-T in the presence of acidified potassium bromide, the end-point being shown by the decolorization of the methyl red indicator. Nitrate, copper(II), mercury(II), etc. are found not to interfere, and the determination of nitrite in the presence of diazotized aromatic amines is demonstrated.

Single organic compounds can be determined by a wide variety of methods but problems may arise in the analysis of individual substances in mixtures or in the presence of interfering substances [l]. Procedures are described in this paper for the analysis of mixtures of sulphonamides in drug formulations without any preseparation of their constituents. Because of the extensive use of sulphonamides in the treatment of bacterial infections, their determination in formulations, either alone or in mixtures with other sulpha drugs, has received considerable attention [2-71. The official sulphonamides are all derivatives of sulphanilamide and are analysed by diazotization of the aromatic amino group [8,9]. However, sulphafurazole has been reported to consume more than one equivalent of nitrite [9, lo]. Drug excipients that are acidic interfere with the alkalimetric titration of sulphonamides [ll-1.51, e.g. with diiodohydroxyquinoline. Titration with bromine has been recommended [16-191 but this technique is not widely used mainly because of the varying stoichiometry of the reaction [20-241. In theory, four equivalents of bromine are consumed in the substitution at both positions ortho to the aromatic amino group. However, it has been found that certain substituents attached to the sulphonamido sidechain also take up two equivalents of bromine. The ortho-dibromination is prevented by acetylation of the aromatic amino group as a result of its steric and electronic deactivation factors but bromine consumption by the side-chain substituent remains unaffected. Similar deactivation effects have also been observed when the amino group is diazotized. These two prereactions permit the analysis of acylated and non-acylated sulphonamides and other sulpha drugs when present in the same sample.

Thiol groups are titrated directly with o-iodosobenzoate reagent at pH 7 employing leuco-2, 6-dichlorophenolindophenol with potassium iodide as indicator. This modification avoids errors that result from side-reactions of iodine, which take place if the excess of iodosobenzoate is made to react with acidified potassium iodide.

Periodate has been determined at the p.p.m. level by it's reaction between pH 7 and 8.5 with amodiaquine dihydrochloride [7-chloro-4-(3′-diethylaminomethyl-4′-hydroxylanilino)quinoline dihydrochloride] which yields a chromogen believed to be a 1,4-benzoquinoneimine. The chromogen is extracted into chloroform for spectrophotometric measurement. The maximum molar absorptivity at 442 nm is 2.03 × 103 l mol–1 cm–1 and Beer's law is valid over the concentration range 10–60 p.p.m. with an over-all relative standard deviation of 0.7%. No interference is caused by a 100-fold (m/m) excess of iodate and this has enabled the method to be used for the indirect determination of ethylene glycol, glycerol and tartaric acid via the Malaprade reaction.

This paper describes some improvements in bromimetric titrimetry which are based on the determination of bromide and its oxidation products formed in the reaction instead of residual bromine. These modifications are particularly applicable to compounds capable of undergoing substitution or oxidation reactions. Substances which only undergo addition reactions do not affect the determination. The determination of bromide is based on oxidation with chloramine T to bromine in the presence of acetanilide, which acts as a bromine scavenger; the residual chloramine T is then determined. The bromine oxidation products of certain organic and inorganic compounds formed on reaction with excess bromine can be determined iodimetrically after the destruction of unreacted bromine with acetanilide. The methods have been tested for the determination of (i) bromide in pharmaceuticals, (ii) a variety of organic compounds through bromide formation (e.g., hydrazine, thiourea, allylthiourea, cystine, homocystine, methionine, phenol and aniline), (iii) certain substances through their oxidation product with bromine (e.g., cyanide, thiocyanate, thallium, 4-aminophenol, hydroquinone, 4-anisidine and thiosemicarbazide) and (iv) mixtures of thiocyanate and cyanide (in polluted water), hydroquinone, thiocyanate and metol (in photographic developers) and phenacetin and paracetamol (in drugs).

Paracetamol (N-acetyl-4-aminophenol) undergoes oxidation with 2-iodylbenzoate in acid medium, producing an orange-yellow colour that attains maximum intensity within 1 min and absorbs maximally at 444 nm. Determination is made either by adding an excess of the reagent to paracetamol and measuring the colour spectrophotometrically or by titrating the test solution photometrically with standardised 2-iodylbenzoate. The Sandell sensitivity is 0.232 µg cm–2 of paracetamol and the method is suitable for routine analysis and unaffected by the presence of salicylamide, oxyphenbutazone, analgin and a number of other excipients.