Fluorometric determination of non-fluorescent amines by ion-pair extraction

Summary An ion pair extraction method is described for quantitative fluorometric determination in the ng/ml range of non-fluorescent amines used as drugs. As counter ion, reagent, anthracene-2-sulphonate was used. Its extracting ability of ion pairs with amines was studied by determination of extraction constants and its fluorescence properties by determination of quantum yield of fluorescence. The properties of a suitable organic solvent is discussed and methylene chloride was found to be advantageous. Conditions for quantitative extraction and determination are given and the method was applied to determination of amitriptyline in the range 10–100 ng/ml giving an extraction degree of 100% and a precision of 5%.

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Fluorimetrische Bestimmung nicht fluorescierender Amine durch Ionenpaarextraktion

Zusammenfassung Die untersuchten Amine finden Verwendung als Arzneimittel und können in Mengen von ng/ml bestimmt werden. Anthracen-2-sulfonat dient als Gegenion. Die Eignung zur Ionenpaarextraktion wird durch Bestimmung der Extraktionskonstanten geprüft. Die Fluorescenzeigenschaften werden durch Messung der Quantenausbeuten der Fluorescenz bestimmt. Die erforderlichen Eigenschaften eines Lösungsmittels werden diskutiert. Methylenchlorid erweist sich dabei als gut geeignet. Die Bedingungen für quantitative Extraktion und Bestimmung werden angegeben. Die Methode wurde für die Bestimmung von Amitriptyline im Bereich 10–100 ng/ml ausgearbeitet, wobei sich ein Extraktionsgrad von 100% und eine Präzision von 5% ergaben.

     

Liquid-liquid extraction with long-chain quaternary Ammonium Halides

The extraction of anionic chloro-complexes of certain metal ions using various long-chain quaternary ammonium halides in toluene and chloroform is described. The investigation has concerned itself mainly with coualt(II) and iron(III); a few extractions have also been carried out with indium(III) and gallium(in). The ion association of chloro-anionic complexes of iron, cobalt, indium and gallium in aqueous chloride media (hydrochloric acid or lithium chloride) with the quaternary ammonium ion in the organic phase is responsible for the extraction of the metal ion into the organic phase. Tlic extraction efficiency varies with the nature of the metal ion system involved as well as with the distribution of the quaternary compound and the size, shape and nature of the organic groups substituted in the quaternary compound.     

Simultaneous two- and three-component determinations in multicomponent mixtures by extraction-spectrophotometry and thermochromism of ion-association complexes

A selective method of determination of amines and quaternary ammonium salts by solvent extraction and thermochromism of ion-association complexes has been established. The method is based on the formation of ion-association species with tetrabromophenolphthalein ethyl ester and the thermochromism effect in the organic phase at low temperature. The absorbance of the red amine charge-transfer complexes decreases quantitatively (DeltaA) with increase in temperature (DeltaT), and Delta A Delta T is characteristic of a particular species. This characteristic has been applied for the sensitive and selective determination of amines. The absorbance of the blue quaternary ammonium ion-association complexes does not vary with temperature, however, and the quaternary ammonium compounds can be determined without interference by amines because of the disappearance of the red species at 60 degrees . Methylephedrine, diphenhydramine, ephedrine (amines), benzethonium and/or berberine (quaternary ammonium compounds) in two- and three-component mixtures can be determined by using the thermochromism effect. The method is highly selective, sensitive and reproducible.     

Reversed-phase ion-pair partition chromatography of carboxylates and sulphonates.

A reversed-phase partition chromatographic system for separation of organic anions as ion pairs with quaternary ammonium ions has been developed. Commercial, hydrophobized silica supports are used with 1-pentanol as stationary phase and aqueous solutions of tetrabutylammonium (TBA) as mobile phase. The separation of the aromatic sulphonates and benzoic acid derivatives is demonstrated. The use of the TBA concentration of the mobile phase to regulate the capacity factor of the anions, as a means of improving separation by gradient elution and direct injection of large sample volumes, is demonstrated. The isolation of nicotinic acid from human serum samples is shown.     

Stepwise determination of quaternary ammonium salts and aromatic amines in pharmaceuticals by ion association titration.

A stepwise titrimetric method has been developed for the simultaneous determination of pharmaceutical quaternary ammonium salts (R4N+) and aromatic amines (R3N). The method is based on the solvent extraction of R4N+ and R3NH+ with an ion association reagent. Sodium tetrakis(4-fluorophenyl)borate and sodium tetraphenylborate were used as titrants and potassium tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. The ion associate which formed between R4N+ ion and TBPE made a blue color in 1,2-dichloroethane, while the ion associate formed between R3NH+ and TBPE showed a red-violet one. Sample solutions containing quaternary ammonium and/or amine compounds were titrated with sodium tetrakis(4-fluorophenyl)borate or sodium tetraphenylborate. When one drop of excess titrant was added, the color of the organic phase turned from blue or red-violet to yellow at the equivalence point. On the other hand, in the mixture of R4N+ and R3N, the color changed from blue to red-violet at the first equivalence point, and then its color turned to yellow at the second equivalence point. The quaternary ammonium compound and aromatic amine in pharmaceuticals could be simultaneously and successfully determined by the proposed titration method.     

Kinetics of ion-pair extraction in continuous flow systems

Kinetic aspects of ion-pair extraction in continuous-flow systems have been studied. Processes have been developed by using a new methodology based on reversal of the flow direction for a preselected number of cycles and on contiuous monitoring at the detector of a plug of organic phase inserted into a carrier stream (aqueous phase) by means of a conventional injection valve. The configuration used required none of the units typically associated with this separation technique. The information obtained, with clear kinetic connotations, can also be exploited for analytical purposes. The behaviour of different ion pairs formed between ferroin and 23 anionic counter ions has been studied. Individual and joint kinetic determinations of these anions from kinetic parameters are proposed.     

Determination of oxybutinin chloride in pharmaceuticals by reversed-phase ion-pair liquid chromatography with two counter-ions in the eluent

A reliable stability-indicating method using reversed-phase ion-pair high-performance liquid chromatography for the determination of the anticholinergic drug oxybutinin chloride in pharmaceuticals is reported. Sample extraction is easy and fairly rapid and recovery and precision of the method are excellent. Due to the simultaneous use of an organic amine and of an alkanesulphonate in the mobile phase, good selectivity towards related (quaternary ammonium) anticholinergic drugs was obtained.     

Indirect detection in reversed-phase liquid chromatography: Ion-pair retention models for cations on polystyrene polymers

Summary The distribution equilibria of cationic compounds in reversed-phase chromatographic systems (ion-pair chromatography) have been studied on the basis of their effect on a detectable mobile phase component. The solid phase was a polystyrene-divinylbenzene copolymer and the detectable component, a quaternary ammonium ion, 1-methylpyridine. The solutes were mono- and divalent amines and quaternary ammonium ions. The cations can be retained by ion-pair adsorption and ion exchange. Expressions for the ion-pair retention of the solutes and the mobile phase cation (system peak) have been developed assuming Langmuir distribution of ion pairs to a solid phase with one kind of binding site. The validity of the expressions has been tested by evaluation of ion-pair distribution constants using non-linear curve fitting techniques. Good agreement for the constants of common ion pairs was obtained from different kinds of capacity ratio expressions. Ion exchange retention can appear beside ion-pair retention, and it has been observed in the pH range 1.6–6.1. The effect depends not only on cations in the mobile phase, but also on the nature of the buffering systems.     

Anwendung der Substöchiometrischen Verdrängung in Ionen-Assoziations-Systemen Für die Aktivierungsanalyse

The possibility of substoichiometric displacement in ion association systems of metal halogenide anions (chlorides and iodides) and extraction reagent cations is demonstrated. Tetrephenylarsonium halogenide, ternary amines and quaternary ammonium halogenides were used as extraction reagents. The method was applied to the determination of several impurities in aluminium by activation analysis.     

Direct, sensitive and selective detection of free fatty acids by high-performance liquid chromatography with post-column ion-pair extraction and absorbance detection

Free fatty acids (C8-C18) are separated by reversed-phase liquid chromatography and detected using a simple post-column dynamic extraction system in which the acids are extracted as ion pairs with chloroform from the aqueous acetonitrile (gradient: 79-99% acetonitrile) mobile phase after the post-column addition of aqueous Methylene Blue solution. The chloroform phase containing the ion pairs is monitored with an absorbance detector at 651 nm. The detection limits ranged from 26 to 83 ng, depending upon the acid, with coefficients of variation of 1.2-14%. Application of the method to butter and margarine samples permitted detection of free fatty acids down to 35 ppm and in orange juice, down to 0.5 ppm using only an organic solvent extraction without further sample clean-up for isolation of the fatty acids.     

The extraction of alkoxide anions by quaternary ammonium phase transfer catalysis

Only trace amounts of hydroxide ion can be extracted from aqueous solution into non-polar organic media by quaternary ammonium salts. Addition of small amounts of primary alcohols, particularly certain diols, dramatically changes the behaviour of systems, and surprising amounts of base can be found in the organic apolar phase. The competitive extraction halide/alkoxide was investigated for various ammonium salts. Quantitative measurements were carried out for the evaluation of selectivity constants for extraction of simple primary alkoxides by tetra-n-hexylammonium chloride in benzene.     

Separation of tungsten from molybdenum by liquid-liquid extraction and extraction chromatography using thiocyanate and a quaternary ammonium salt

Methods were developed for the separation of tungsten from molybdenum by liquid-liquid extraction and extraction chromatography using thiocyanate and a quaternary ammonium salt, Zephiramine. Tungsten was extracted into chloroform as an ion associate of tungsten(V)-thiocyanate complex and Zephiramine cation was retained on a column of Teflon powder coated with Zephiramine, but molybdenum(III) was neither extracted nor retained. The extraction chromatographic method was successfully applied to the determination of trace amounts of tungsten in molybdenum by neutron activation analysis.     

Photometric determination of quaternary ammonium compounds with hexanitrodiphenylamine. II

In strongly alkaline medium (more than 0.1 N NaOH) hexanitrodiphenylamine anion reacts with base. The reaction is rather slow and is partly reversible.Quaternary ammonium ions can be determined by extraction of their hexanitrodiphenylamine complexes with chloroform or methylene chloride at pH 11 or with methylene chloride from 3N NaOH. Only the latter method is applicable to compounds containing several quaternary ammonium groups. The compounds extracted have high molar extinction and good stability. Quaternary ammonium ions can be determined in the presence of amines, and in some cases determination of quaternary ammonium ions in admixture is possible.     

Analysis of propantheline bromide and related quaternary ammonium drugs by reversed-phase,ion-pair liquid chromatography with two counterions in the eluent

Summary The addition of appropriate concentrations of an organic amine and an alkylsulphonate to the mobile phase in reversed-phase, ion-pair liquid chromatography can introduce unique selectivity in to the chromatographic system allowing separation of complex mixtures of basic, acidic and neutral compounds. As an example, the methodology for a specific stability-indicating determination of propantheline bromide, a quaternary ammonium anticholinergic agent, on several reversedphase stationary phases, was developed. The retention mechanism was studied and it was concluded that both ion-interaction processes and ion-exchange processes were involved in the separation technique developed with two counterions of opposite charge in the eluent.     

Ion-pair hollow-fiber liquid-phase microextraction of the quaternary ammonium surfactant dicocodimethylammonium chloride

A two-phase hollow-fiber (HF) liquid-phase microextraction (LPME) method was developed for determination of a quaternary ammonium compound surfactant, dicocodimethylammonium chloride, in aqueous samples. The porous HF was fixed on a metal rod support and was impregnated with approximately 6.6 μL of organic extractant, which was immobilized in the HF pores. Surfactant extraction was facilitated by addition of carboxylic acid to the sample forming neutral ion pairs with the quaternary ammonium compound. After extraction, the analyte was transferred from the organic extractant in the fiber pores by dissolving the 1-octanol into 100 μL methanol. The methanol extract was analyzed by liquid chromatography–mass spectrometry. The method was optimized (with optimized parameters in brackets) with regard to type of organic extractant (1-octanol), fiber length (2 cm), choice and concentration of anionic carrier (600 μg L⁻¹ octanoate), procedure of transfer to methanol (15-min sonication), sample volume (250 mL), extraction time (17 h), pH (10), and ionic strength (50 mM carbonate). Aspects influencing repeatability in LPME of (quaternary ammonium) surfactants are discussed. The enrichment factor achieved in 250-mL carbonate buffer was around 400. Due to matrix effects, the enrichment factors achieved when industrial process water was analyzed were 120 or about 30% of that in carbonate buffer. Detection limits of 0.3 μg L⁻¹ in carbonate buffer and 0.9 μg L⁻¹ in industrial process water were obtained. If the studied compound is seen as a model substance representing quaternary dialkylated dimethylated ammonium surfactants in general, the developed method may be applied to other quaternary ammonium surfactants.     

Synthesis of Chiral Resorcinarene-based Hosts and a Mass Spectrometric Study of their Chemistry in Solution and the Gas Phase

The syntheses and characterization of new chiral tetrabenzoxazine and tetrakis-(dialkylaminomethyl) resorcinarenes can be achieved through the reaction of resorcinarene with chiral amines and formaldehyde. In order to examine their host–guest chemistry, chiral quaternary ammonium guests were synthesized by methylation of different amines and amino acid methyl esters through a reductive methylation followed by addition of methyl iodide. Subsequent anion exchange of the iodide against tetraphenylborate helps to improve solubility of the salts in organic solvents. After characterization in solution, mass spectrometry is used to examine the resorcinarenes’ chemistry in the gas phase. Interesting implications of the fragmentation behavior for their solution phase chemistry arise, for which a first example is presented. Ammonium ion binding is indicated by mass spectrometry. Nevertheless, chiral recognition between the chiral hosts and pseudoracemic 1:1 mixtures of appropriately deuterium-labeled chiral guest cations is however not observed.     

Unexpected Hofmann elimination in the benzophenone-(phenylthio)acetic tetrabutylammonium salt photoredox system

The triplet state of benzophenone was quenched by the tetrabutylammonium salt of (phenylthio)acetic acid in acetonitrile solutions. The quenching event, following laser flash photolysis, resulted in the formation of a transient ion pair consisting of the benzophenone radical anion and the tetrabutylammonium cation. Subsequently this ion pair decays with the quaternary ammonium cation undergoing a Hofmann elimination to form butane-1 and tributylamine, which were detected in steady-state irradiation. This appears to be the first report of an ion pair consisting of a benzophenone radical anion and an organic cation (nonradical), in addition to the first report of a photoinduced Hofmann elimination in quaternary ammonium ions.     

Liquid-liquid distribution of ion associates of hexachloroplatinate(IV) with quaternary ammonium counter ions

The distribution behavior of ion associates of PtCl(6)(2-) with quaternary ammonium cations (Q(+)) between aqueous phase and two organic phases (chloroform and carbon tetrachloride) was examined, and the extraction constants (log K(ex)) were determined. A linear relationship was found between log K(ex) and the total number of carbon atoms in Q(+); from the slope of the line, the contribution of a methylene group to log K(ex) was calculated to be 0.6. The extractability with alkyltrimethylammonium cations was larger than that with symmetrical tetraalkylammonium cations. From the extraction constants obtained, an extraction method based on the ion association of PtCl(6)(2-) with Q(+) can be used for the separation and determination of platinum at the 10(-6) M level.     

A new method of removing excess of reagent from organic phases in the solvent extraction of metal complex anions with quaternary ammonium salts: Spectrophotometric determination of micro amounts of cobalt with 2-nitroso-1-naphthol-4-sulfonic acid

The removal of excess reagent extracted into an organic phase in the solvent extraction of a metal complex anion with a quaternary ammonium ion is discussed. With a given chelating ligand (HO—R—SO₃H), the order of extractability is HO—R—SO₃^- > M(OR—SO₃)^n- > X^- > ^-O—R—SO₃^- when an anion such as nitrate or halide is added. If suitable amounts of the anion are added, only the excess of reagent can be removed. The principle is applied to the extraction with zephiramine of the cobalt complex anion formed with 2-nitroso-1-naphthol-4-sulfonic acid. Micro amounts of cobalt in pure nickel salts were determined spectrophotometrically.     

A high performance liquid chromatographic post-column fluorescent ion pair extraction system: application to physostigmine and its metabolite eseroline in human serum

A high performance liquid chromatographic post-column fluorescent ion pair extraction system was developed for the analysis of quaternary ammonium and amine drugs in serum. A new fluorescent ion pair reagent, sodium alpha-(3,4-dimethoxyphenyl) cinnamonitrile-2'-sulfonate (DPS), was synthesized and characterized. The post-column extraction system consisted of a three-dimensional knitted teflon mixing coil and a membrane phase separator which was modified from an original literature design. Physostigmine and its metabolite eseroline were used as model cations. A solid phase extraction procedure using octadecylsilane columns was developed to extract the compounds and neostigmine bromide (internal standard) from human serum. The compounds were chromatographed on a diol column using a 80:20 aqueous phosphate buffer pH 4 absolute methanol mobile phase at a flow rate of 1 mL/min. Methylene chloride was used as the on-line extraction solvent for the DPS ion pairs formed. Fluorescence of the extracted ion pairs was measured using an excitation of 243 nm and an emission cut-off filter at 418 nm. Linearity was in the 2-100 ng/mL and 5-100 ng/mL ranges for physostigmine and eseroline, respectively. Detection limits based on a signal-to-noise ratio of 2, were 2 and 5 ng/mL, respectively. Precision of the method was found to be in the 1.5-3% range and percentage error in the 1.5-7% range for both compounds.