Spectrophotometric and atomic absorption spectrometric determination of ramipril and perindopril through ternary complex formation with eosin and Cu(II)

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of ramipril and perindopril. Both methods are based on the formation of a ternary complex, extractable with chloroform, between copper(II), eosin and the two cited drugs. Spectrophotometrically under the optimum condition, the ternary complexes showed an absorption maximum at 535 nm, with apparent molar absorptivities of 6.55 and 4.00×10³ mol⁻¹cm⁻¹ and Sandell’s sensitivities of 5.80×10⁻² and 1.04×10⁻¹μg cm⁻² for perindopril and ramipril, respectively. The solution of ternary complex obeyed Beer’s law in concentration ranges 10–60 and 20–100 μg ml⁻¹ for perindopril and ramipril, respectively. The proposed method was applied to the determination of the two cited drugs in pharmaceutical tablets. The atomic absorption spectrometric method, directly through the quantitative determination of copper content of the organic extract of the complex, was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and perindopril dosage forms.     

Use of palladium(II) chloride as colour-forming reagent in determination of pralidoxime chloride in water and tablets

Pralidoxime chloride (PAM-2Cl) has been determined spectrophotometrically in Britton—Robinson buffer solution at pH = 6.45; the method is based on measurement of the absorbance of the Pd(II)-pralidoxime complex at 327 nm. Studies of the composition of the complex by Job's continuous variation method, the molar ratio method and Bent—French's method yielded a Pd(II):pralidoxime ratio of 1:1. The conditional stability constant (K′) of the complex at the optimum pH of 6.45 and an ionic strength (μ) of 0.3 M was found to be 10^5.2. The molar absorptivity was 1.05 × 10⁴ 1 mol⁻¹ cm⁻¹. Beer's law was obeyed at concentrations up to 60 μM. The detection limit was 0.55 μg ml⁻¹. The relative standard deviation (N = 10) was 0.28–1.03%. The method was accurate and sensitive for the analysis of PAM-2Cl in water and tablets.     

Spectrophotometric determination of pefloxacin in pharmaceutical preparations

It has been established that the antibiotic pefloxacin (Abaktal) methane-sulphonate reacts with Fe(III) at pH 1.00–8.00 to form a water-soluble complex with maximum absorbance at 360 nm. The composition of the complex, determined spectrophotometrically by the application of Job's, molar-ratio and Bent—French's methods, was pefloxacin: Fe(III) = 1:1 (pH = 2.50; λ = 360 nm; μ = 0.1 M). The relative stability constant, obtained by the methods of Sommer and Asmus was 10^5.02 (pH = 2.50; λ = 360 nm; μ = 0.1 M). The molar absorptivity of the complex at 360 nm was found to be 4.8 × 10³ l mol⁻¹ cm⁻¹, Beer's law was followed for pefloxacin concentrations of 2.15–85.88 μg ml⁻¹. The lower sensitivity limit of the method was 2.15 μg ml⁻¹. The relative standard deviation (n = 10) was 0.57–1.07%. The method can be applied to the rapid and simple determination of pefloxacin in aqueous solutions and tablets.     

Spectrophotometric study of polythiazide—palladium(II) complex

A quantitative spectrophotometric method using Pd(II) chloride as analytical reagent for the determination of polythiazide in pharmaceutical preparations is described in this study. It has been found that polythiazide reacts with Pd(II) chloride in the pH range 3.6–5.8, forming a red, water-soluble (1:1) complex with maximum absorbance at 527 nm. At the optimum pH of 4.8 and an ionic strength μ = 0.1 M, the conditional stability constant of the complex is found to be log K′ = 4.77. The molar absorptivity at 527 nm is 3.2 × 10³ 1 mol⁻¹ cm⁻¹. Good agreement with Beer's law was found for polythiazide concentrations up to 2.2 mmol l⁻¹. The nominal percent recovery of polythiazide was 99.5% (n = 20). The simplicity, selectivity and sensitivity of the method described is suitable for rapid and accurate determinations of polythiazide in tablets.     

Aminopterin—Monoclonal antibody conjugates: antitumor activity and toxicity

Drug-antibody conjugates are undergoing close scrutiny as new antitumor agents because they confer increased drug specificity, producing higher accumulation in the tumor and less systemic toxicity than free drug. Consequently this has led to the use of drugs more toxic than those that can normally be used. How-ever, contrary to these conclusions immunoconjugates containing aminopterin (AMN), while having potent antitumor activity, are more toxic than free drug. AMN, a more toxic analog of the folic acid antagonist methotrexate (MTX), was coupled to the anti-Ly-2.1 antibody and the in vivo activity of the conjugate was tested against the Ly-2.1⁺ murine thymoma ITT(1)75NS E3 (E3). The aminopterin conjugates had molar ratios of 4-6 residues of AMN per MoAb molecule and retained 50% of the original antibody activity. A single dose of 75 μg AMN-anti-Ly-2.1 inhibited tumor growth by 30% and injection of 105 μg AMN-MoAb conjugate, in three doses, caused 63% tumor growth inhibition. Considerably higher doses of free AMN are required to produce similar tumor inhibition. Injection of 90 μg AMN-anti-Ly-2.1 or 900 μg free AMN produced signs of toxicity or death in the mice. Hematological examination revealed severe depletions in white blood cell (control, 7.71 × 10³/μl; AMN, 3.39 × 10³/μl; and AMN-anti-Ly-2.1, 1.29 × 10³/μl and platelet (control, 501.6 × 10³/μl; AMN, 234.7 × 10³/μl; and AMN-anti-Ly-2.1, 157.1 × 10³/μl) numbers for free and conjugated forms of AMN. Histological and hematological examinations indicate that there are similar sites of toxicity after AMN and AMN-MoAb conjugate treatment. The studies showed that the AMN-anti-Ly-2.1 conjugate is a potent antitumor agent and is capable of reducing the growth of subcutaneous tumors.     

The effect of trimethyltin on acetylcholine release in the guinea-pig trachea

The purpose of the present work was to characterise the effects of trimethyltin on the release of acetylcholine from parasympathetic nerves and its effect on the postjunctional cholinergic stimulation of a smooth muscle. The guinea-pig trachea has been used as a model. Prejunctionally, trimethyltin (3.0 × 10⁻³ M) significantly enhanced in a reversible manner the high K⁺ (75 mM) evoked release of endogenous acetylcholine and [³H]acetylcholine. The evoked release of endogenous acetylcholine and [³H]acetylcholine was released from a pool of acetylcholine being independent of extraneuronal Ca²⁺ in the presence, but not in the absence of trimethyltin. The effect of trimethyltin on the release was not inhibited by low Ca²⁺ (0 mM and 1.0 × 10⁻⁴ M) or by Ca²⁺ channel blockers (verapamil, 1.0 × 10⁻⁴ M, flunarizine, 1.0 × 10⁻⁴ M, ω-conotoxin GVIA, 2.0 × 10⁻⁷ M and ω-agatoxin, 2.0 × 10⁻⁷ M). The present results also demonstrate that trimethyltin induce emptying of a non-vesicular, probably a cytoplasmic storage pool of acetylcholine, since AH5183 (2.0 × 10⁻⁵ M), an inhibitor of the translocation of acetylcholine into synaptic vesicles, and -latrotoxin (1.0 × 10⁻⁸ M), a toxin from black widow spider venom inducing vesicle depletion, had no inhibitory effects on the release of [³H]acetylcholine evoked by trimethyltin (3.0 × 10⁻³ M). The release of [³H]acetylcholine was moreover enhanced by trimethyltin when the vesicular uptake of [³H]acetylcholine was inhibited by AH5183, probably as a result of a higher cytoplasmic concentration of [³H]acetylcholine. Trimethyltin also reduced the neuronal uptake of [³H]choline and this was probably due to a depolarising effect of trimethyltin on the cholinergic nerve terminals. A similar depolarisation induced by trimethyltin was observed during patch clamping of GH₄ C₁ neuronal cells. Postjunctionally, trimethyltin had no effect by itself or on the carbachol-induced smooth muscle contraction, indicating that trimethyltin did not have a general depolarising effect on smooth muscle cells or an effect on muscarinic receptors. Furthermore, the reduced electrical field-induced contraction and the subsequent increase in the basal smooth muscle tension that was observed by addition of trimethyltin was activity-dependent, and was most probably due to emptying of a nervous non-vesicular storage pool of acetylcholine, followed by rapid hydrolysis of acetylcholine by acetyl- and pseudocholinesterases.     

A rapid colorimetric method for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage form

Two new rapid reproducible and economical spectrophotometric methods are described for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage forms. Both methods are based on the formation of an orange-red and orange ion-pair complex due to the action of Calmagite (CT) and Orange-II (O-II) on Losartan potassium in acidic medium (pH 1.2). Under optimised conditions, they show an absorption maxima at 491 nm (CT) and 486 nm (O-II), with molar absorptivities of 1.74×10³ and 1.75×10³ l mol⁻¹ cm⁻¹ and Sandell's sensitivities of 0.2649 and 0.2637 per 0.001 absorbance unit for CT and O-II, respectively. The colour is stable for 5 min after extraction. In both cases Beer's law is obeyed between 10 and 100 μg ml⁻¹. The proposed method was successfully extended to synthetic mixture for solid dosage forms.     

Spectrophotometric determination of oxytetracycline in pharmaceutical preparations using sodium molybdate as analytical reagent

A spectrophotometric method is proposed for the determination of oxytetracycline in pharmaceutical preparations. The method is based on the measurement of the absorbance of the molybdate—oxytetracycline complex at 404 nm (pH 5.50; μ = 0.1 M; 20°C). The composition of the complex (1:1) was determined by the application of the spectrophotometric methods of Job and Bent—French (pH 5.50; λ = 390 nm; μ = 0.1 M). The relative stability constant (K′ = 10^4.6) of the complex was obtained by the methods of Sommer and Nash (pH 5.50; λ = 390 nm; μ = 0.1 M; 20°C). The molar absorptivity of the complex was 9.5 × 10³ l mol⁻¹ cm⁻¹. Beer's law was obeyed over the concentration range 2.48–34.78 μg ml⁻¹. The relative standard deviation RSD (n = 10) was 0.27–0.39%. The method proposed can be applied to the assay of oxytetracycline in capsules. The detection limit of oxytetracycline is 2.5 μg ml⁻¹.     

Characterization of polymethoxylated flavones in Fructus aurantii by liquid chromatography with atmospheric pressure chemical ionization combined with tandem mass spectrometry

Atmospheric pressure chemical ionization mass spectrometry (APCI-MS) was operated in positive mode (PI) to characterize polymethoxylated flavonoids (PMFs) through its specific radical cations by collision-induced dissociation (CID). The fragments of [M + H − n × 15]⁺ produced by loss of one or more methyl group from the protonated molecule, as well as [M + H − 29]⁺, [M + H − 31]⁺, [M + H − 33]⁺, [M + H − 43]⁺, [M + H − 46]⁺, and [M + H − 61]⁺ fragment ions were detected, which were diagnostic for the polymethoxylated species, and could be adopted to form the multiple MS (MSⁿ) “fingerprint” of PMFs. Based on this “fingerprint”, 29 PMFs were screened out from extracts of Fructus aurantii, among which two of them were identified as sinensetin and tangeretin. It was proved that the PI was suitable for structural characterization of PMFs by APCI-MSⁿ.     

The action of trelibet, a new antidepressive agent on [H]noradrenaline release from rabbit pulmonary artery

Trelibet, a new antidepressant, used at 10⁻⁷–10⁻⁴ M failed to affect the [³H]noradrenaline ([³H]NA) release evoked from the isolated main pulmonary artery of the rabbit low frequency (2 Hz) nerve stimulation whether the neuronal uptake inhibitor cocaine (3 × 10⁻⁵ M) was present or not. Its metabolite (EGYT-2760) however, potentiated the nerve-evoked release of [³H]NA. In the absence of cocaine both the resting and the stimulation-evoked release of ³H increased in response to EGYT-2760. These effect were accompanied by muscle contraction. The EGYT-2760-potentiated transmitter release was inhibited either by exogenously applied 1-noradrenaline (10⁻⁶ M) or clonidine (10⁻⁶ M), preferential agonists of presynaptic ₂-adrenoceptors. The 1-noradrenaline-induced inhibition of transmitter release potentiated by EGYT-2760 was antagonized by 3 × 10⁻⁷ M yohimbine, a preferential ₂-adrenoceptor inhibitor. In the absence of cocaine, Ca²⁺ removal from the external medium failed to affect the ³H outflow-increasing effect of EGYT-2760 but abolished the nerve-evoked release-potentiating action of this compound. It is concluded that the metabolite of trelibet exerts a ‘yohimbine-like’ action, as well as a ‘tyramine-like’ effect in peripheral sympathetic nerve fibres.     

Flow injection and HPLC determination of furosemide using pulsed amperometric detection at microelectrodes

The flow-injection and HPLC determination of the diuretic drug furosemide using pulsed amperometric detection (PAD) at cylindrical carbon fibre microelectrodes (CFMEs) is reported. Experimental conditions such as pH (6.5) and buffer concentration (0.05 mol l⁻¹ HPO₄²⁻/H₂PO₄⁻) were optimized using square-wave voltammetry (SWV). Repetitive flow-injection amperometric measurements at +1.25 V for furosemide showed a continuous decrease in the peak current, probably as a consequence of the microelectrode surface fouling. However, a suitable amperometric detection of furosemide was achieved using a PAD program consisting of a two-step potential waveform with alternating anodic and cathodic polarization. The anodic (detection) potential was +1.25 V (time of application 0.1 s), and the cathodic (cleaning) potential was −0.20 V (t=0.2 s). A linear calibration graph was obtained for furosemide in the 5.0×10⁻⁷–1.0×10⁻⁴ mol l⁻¹ concentration range, with a limit of detection of 1.7×10⁻⁷ mol l⁻¹. HPLC-PAD at carbon fibre microelectrodes was used for the determination of furosemide in the presence of several thiouracil drugs and oxytetracycline (OTC). The mobile phase selected was a 25:75 acetonitrile:5.0×10⁻³ mol l⁻¹ NaH₂PO₄ (pH 5.0) mixture. A linear calibration graph was obtained for furosemide in the 1–100 μM range, with a limit of detection of 0.55 μM. The usefulness of this method for the determination of furosemide in real samples was evaluated by performing the analysis of commercial milk samples spiked with furosemide at a concentration level of 4.5×10⁻⁷ mol l⁻¹ (150 ng ml⁻¹), as well as with other thiouracil drugs and OTC. A mean recovery of 95±5% furosemide was obtained.     

Polarographic determination of diazepam with its parallel catalytic wave in the presence of persulfate

A new method for the determination of diazepam was proposed based on its polarographic catalytic wave in the presence of persulfate. In 0.20 M NaAc–HAc (pH 4.7)–2.0×10⁻² M K₂S₂O₈ supporting electrolyte, the reduction wave of diazepam with peak potential −0.89 V (versus SCE) was catalyzed, producing a parallel catalytic wave. The peak current of the catalytic wave was 15 times higher than that of the corresponding reduction wave for 4.0×10⁻⁶ M diazepam, and was rectilinear to diazepam concentration in the range of 5.6×10⁻⁸ to 8.8×10⁻⁶ and 8.8×10⁻⁶ to 2.0×10⁻⁴ M. The detection limit was 9.6×10⁻⁹ M. The mechanism of the parallel catalytic wave of diazepam was discussed.     

Flow injection spectrophotometric determination of Al in hemodialysis solutions

A flow analysis (FA) system with spectrophotometric detection for Al determination in hemodialysis solutions was developed. The method was based on the reaction of Al with eriochrome cyanine R (ECR). The complex formed associated with cetyltrimethylammonium bromide (CTAB) — a cationic surfactant, which showed enough sensitivity to execute the direct analyte determination. All interferences were eliminated with the matrix matching calibration. The system presented the following analytic parameters: sensitivity (m) of 8.10 × 10⁻⁴ L μg⁻¹, limit of detection (LOD) of 3.24 μg L⁻¹ (3σ), linear correlation coefficient of 0.9966 and linear range response from 10.8 to 650 μg L⁻¹. The accuracy of the proposed method was checked by comparison with electrothermal atomic absorption spectrometry (ET-AAS) method. There were no differences among the results obtained from both methods, at a confidence level of 95% (paired t-test). Recovery tests were also made, values obtained were from 90.4 to 109 of recovery for Al-spiked samples.     

A surface plasmon resonance method for detecting multiple modes of DNA-ligand interactions

A simple and general surface plasmon resonance (SPR) based method has been developed to detect and quantitate binding of low molecular weight compounds (200–1200 Da) to double stranded DNA. Several compounds were chosen to probe three different modes of binding interactions, intercalation, minor groove binding and electrostatic interactions. Ethidium bromide (MW 390 Da), a probe of intercalative binding, was tested by plotting the steady state SPR responses measured on a DNA modified surface versus ethidium bromide concentration. The best fit of the binding isotherm gave a K_eq of 1.8×10⁵ M⁻¹. Co-solvents such as DMSO are often used in activity assays to increase the solubility of poorly water-soluble drugs. The effect of DMSO on the ethidium bromide/DNA interaction was also tested by measuring binding in the presence of 0, 1 and 5% DMSO. No effect on the measured K_eq was observed at these DMSO concentrations. The binding of actinomycin (MW 1255 Da), an antibiotic known to bind DNA through intercalation and minor groove binding, was also tested. The K_eq estimated from the steady state responses on a DNA surface was 1.9×10⁶ M⁻¹. DAPI (MW 350 Da) (4′,6-diamidino-2-phenylindole) a fluorescent probe which binds the minor groove of DNA was also tested and gave a K_eq of 1.8×10⁶ M⁻¹ measured by SPR. Finally, spermine (MW 202) a compound known to bind DNA through ionic interactions gave the weakest K_eq of 1.7×10⁴ M⁻¹. All the K_eq values measured by SPR and reported for these compounds were in good agreement with literature values measured by other techniques.     

Electrochemical detection of DNA immobilized on gold colloid particles modified self-assembled monolayer electrode with silver nanoparticle label

The target DNA was immobilized successfully on gold colloid particles associated with a cysteamine monolayer on gold electrode surface. Self-assembly of colloidal Au onto a cysteamine modified gold electrode can enlarge the electrode surface area and enhance greatly the amount of immobilized single stranded DNA (ssDNA). The electron-transfer processes of [Fe(CN)₆]⁴⁻/[Fe(CN)₆]³⁻ on the gold surface were blocked due to the procedures of the target DNA immobilization, which was investigated by impedance spectroscopy. Then single stranded target DNA immobilized on the gold electrode hybridized with the silver nanoparticle–oligonucleotide DNA probe, followed by the release of the silver metal atoms anchored on the hybrids by oxidative metal dissolution, and the indirect determination of the released solubilized Ag^I ions by anodic stripping voltammetry (ASV) at a carbon fiber microelectrode. The results show that this method has good correlation for DNA detection in the range of 10–800 pmol/l and allows the detection level as low as 5 pmol/l of the target oligonucleotides.     

Utility of formazans and cetylpyridinium chloride in rapid spectrophotometric determination of zinc in biological materials and pharmaceutical formulations

A facile, rapid and sensitive spectrophotometric method for the determination of zinc is performed, based on complexation reaction between the metal ion and 1,5-diphenyl-3-acetylformazan (I) 1-(o-carboxyphenyl)-3-acetyl-5-acetylformazan (II), 1-(o-carboxyphenyl)-3-acetyl-5-phenylformazan (III), and 1-(o-carboxyphenyl)-3-acetyl-5-m-tolylformazan (IV) in the presence of cationic surfactant cetylpyridinium chloride (CPC). The important analytical parameters and their effects on the reported system are investigated. Zinc reacts with the reagents (I-IV) and CPC in the ratio 1:1:2 (metal:reagent:CPC) in the pH range 8.5, 7.5, 5.5 and 6.5 to form a ternary complex with an absorption maximum 616, 656, 672 and 599 nm, respectively. The reaction was extremely rapid at room temperature, and the absorbance value remains unchanged for at least 1 week. The apparent stability constant of the complex were found to be 13.1 9.2, 11.4 and 12.3, and adheres to Beer's law for 0.05-3.50 microg per 10 ml of zinc. For more accurate analysis, Ringbom optimum concentration range was found from 0.08 to 3.20 microg per 10 ml of zinc. The apparent molar absorptivity, Sandell sensitivity, detection and quantification limits are also calculated. Taking a constant concentration of metal ion and determining its concentration in the presence of large number of foreign ions tested the effect of foreign ions. The method was applied for determination of zinc in serum, human hair and pharmaceutical formulations, where excellent agreements between reported and obtained results were achieved. The relative standard deviation was better than 1.67%.     

Purification and partial characterization of two cytolysins from a tropical sea anemone, Heteractis magnifica

Two cytolysins, designated as magnificalysins I and II, were purified from a tropical sea anemone, Heteractis magnifica (formerly Radianthus ritteri). The purification steps involved Sephadex G-50 and CM-Sepharose chromatography followed by Mono S and Phenyl-Superose Fast Protein Liquid Chromatography. The relative mol. wt of magnificalysins I and II, determined by SDS-PAGE, was approximately 19,000, while their isoelectric points, determined by isoelectric focusing in immobilized pH gradients, were 9.4 and 10.0, respectively. Those toxins were found to have haemolytic and lethal activities. The haemolytic activities of magnificalysins I and II were 3.6 × 10⁴ HU/mg and 3.3 × 10⁴ HU/mg, while their ld₅₀ (i.v., mice) values were approximately 0.14 μg/g and 0.32 μg/g, respectively. The amino acid composition and N-terminal sequences of magnificalysins I and II were also obtained. They do not possess any cysteine or cystine residue, but are rich in basic and hydrophobic amino acids. The N-terminal amino acid sequences of magnificalysins I and II are ALAGTIIAGASLTFKILDEV and SAALAGTIIDGASLGFDILNKV, respectively. These are highly homologous to cytolysins from other sea anemones, particularly cytolysin III from Stichodactyla helianthus, a Caribbean anemone.     

NMR studies of the inclusion complex between β-cyclodextrin and paroxetine

A ¹H and ¹³C NMR study on the inclusion complex of paroxetine with β-cyclodextrin was carried out in order to define the stoichiometry of the association and its strength. Proton and carbon chemical shift measurements of paroxetine and β-cyclodextrin were performed at several molar ratios and temperatures, allowing the determination of a 1:1 stoichiometry and an association constant value of the order of 2 × 10³ for the paroxetine–β-cyclodextrin complex. Overhauser effects in the rotating frame were also measured, and the experimental interproton distance constraints have been used for molecular model building of the complex. The obtained model indicates that the benzodioxolyl moiety of paroxetine is deeply inserted in the cavity of the cylindrical structure of β-cyclodextrin, while the fluoro-phenyl ring lays above the wider rim.     

Cellular disposition of arabinogalactan in primary cultured rat hepatocytes

To characterize a targeting property of arabinogalactan (AG) as a carrier to the liver, we examined cellular disposition, such as binding and internalization in primary cultured rat hepatocytes, comparing them to those of asialofetuin (AF). A tyramine derivative of AG was synthesized to allow labeling with ¹²⁵I. Binding of AG to the cells was concentration-dependent and saturable. The number of binding sites (n) of AG on the cell surface was 4.0 × 10⁵ ± 0.1 × 10⁵ sites per cell which was about similar to that of AF. The value of K_a of AG was 2.2 × 10⁸ ± 0.1 × 10⁸ M⁻¹ being seven-fold higher than that of AF. The binding of AG was competitively inhibited by AF and was decreased by calcium depletion. These results indicate that AG can bind strongly to hepatocytes probably through the recognition by the asialoglycoprotein receptor (ASGP-R). Both ¹²⁵I-labeled AG and fluorescein-labeled AG were internalized into the cells. The rate of internalization of AG was faster than that of AF, indicating that AG is effectively endocytosed. Microscopic observations showed that FITC labeled AG accumulated in granules within the primary cultured rat hepatocytes. Subcellular fractionation indicated that the internalized AG was mainly associated with the lysosomal fraction. However, the internalized AG seemed to remain intact in the hepatocytes. In conclusion, we found that AG is effectively internalized in primary cultured rat hepatocytes. Although AG seems a good candidate for targeting to the liver due to its high affinity binding and rapid internalization, it remains to be established whether the apparent lack of biodegradation will result in cytotoxic effects at chronic administration in vivo.     

Cathodic adsorptive stripping voltammetric determination of the anti-inflammatory drug indomethacin

Sensitive voltammetric methods have been developed for the determination of the anti-inflammatory, anti-pyretic and analgesic drug indomethacin sodium. The methods are based on the controlled adsorptive preconcentration of the drug on a hanging mercury drop electrode (HMDE), followed by tracing the voltammogram in a cathodic potential scan. The modes used are cyclic voltammetry (CV), cathodic stripping voltammetry (CSV) and differential pulse stripping voltammetry (DPSV). Amounts as low as 10 nM (10 ng ml⁻¹) (60 s preconcentration) by CSV and 0.5 μM (190 ng ml⁻¹) (300 s) by DPSV can be determined accurately. The R.S.D. at the 1×10⁻⁶ M level is 1.4%. The interference of some metal ions and the application of the method to analysis of urine, plasma and pharmaceutical formulations are described.