Flow injection turbidimetric determination of thiamine in pharmaceutical formulations using silicotungstic acid as precipitant reagent

A simple flow injection system is proposed for the determination of thiamine in pharmaceutical formulations. The determination is based on the precipitation reaction of thiamine with silicotungstic acid in acidic medium to form a thiamine silicotungstate suspension that is measured at 420 nm. Adding 0.05% (w/v) poly(ethyleneglycol) in the carrier solution (0.5 mol l(-1) hydrochloric acid), an improvement in the sensitivity, repeatability and baseline stability of the flow injection system was obtained. The calibration graph was linear in the thiamine concentration range from 5.0x10(-5) to 3.0x10(-4) mol l(-1) with a detection limit of 1.0x10(-5) mol l(-1). The relative standard deviations for ten successive measurements of 1.0x10(-4) mol l(-1) and 2.5x10(-4) mol l(-1) thiamine were less than 1% and an analytical frequency of 90 h(-1) was obtained.     

Determination of thiamine using continuous flow molecular emission cavity analysis

A continuous flow method for the determination of thiamine hydrochloride (20.0-240.0 microgram ml(-1), 5.9 x 10(-5)-7.1 x 10(-4)m) is described. The sample was mixed with an excess of sodium hydroxide and remained in the delay coil for 20 min at 90 degrees C. The solution was then mixed with an excess of orthophosphoric acid and the hydrogen sulphide evolved was transferred continuously into the cavity to generate a molecular++ emission of S2. The analysis is completely automated, requires no sample pre-treatment and samples can be analysed at a rate of 30 samples h(-1) with a relative error of 1-2%. The method was evaluated by carrying out an interference study with common excipients and other water-soluble vitamins, a recovery study and by the analysis of commercial formulations. Results compared well with those obtained using the official method. The method was also applied to content uniformity tests.     

Simultaneous determination of nicotinamide,pyridoxine hydrochloride,thiamine mononitrate and riboflavin in multivitamin with minerals tablets by reversed-phase ion-pair high performance liquid chromatography

A reversed-phase ion-pair high performance liquid chromatographic method (HPLC) has been developed and validated for the routine analysis of nicotinamide, pyridoxine hydrochloride, thiamine mononitrate and riboflavin in multivitamin with minerals tablets. HPLC separation of the vitamins was performed on a Hypersil C(18) column and detected by ultraviolet absorbance at 280 nm. The use of methanol-aqueous 0.5% acetic acid solution (18:82, v/v; containing 2.5 mM sodium hexanesulfonate, pH = 2.8) as the mobile phase at a flow-rate of 1.2 mL/min enables the baseline separation of the four analytes free from interferences with isocratic elution at 30 degrees C. The analysis time was 17 min per injection. The method was linear in the ranges of 5-90, 2.5-90, 5-95 and 25-450 micro g/mL for thiamine mononitrate, riboflavin, pyridoxine hydrochloride and nicotinamide, respectively. The average coefficients of variation of within- and between-day assays were 2.2 and 3.6% for thiamine mononitrate, 1.8 and 2.4% for riboflavin, 1.3 and 1.7% for pyridoxine hydrochloride and 1.0 and 1.5% for nicotinamide, respectively. The average recoveries of thiamine mononitrate, riboflavin, pyridoxine hydrochloride and nicotinamide were 97.0, 97.2, 98.9 and 100.4% for the tablets, respectively. The method has been successfully applied to the simultaneous determination of nicotinamide, pyridoxine hydrochloride, thiamine mononitrate and riboflavin in multivitamin with minerals tablets.     

Electrochemical behavior of thiamine on a self-assembled gold electrode and its square-wave voltammetric determination in pharmaceutical preparations.

The electrochemical behavior of thiamine on a self-assembled electrode of L-cysteine (Cys/SAM/Au) has been investigated and Cys/SAM/Au can be used to detect thiamine using square-wave voltammetry (SWV). At pH 11.40 Britton-Robinson buffer, thiamine exhibits a well-defined anodic peak on Cys/SAM/Au. Under the optimized conditions, the anodic peak current of SWV was linear with the content of thiamine in the range of 1.1 x 10(-8) - 2.2 x 10(-6) mol/L; the detection limit was 5.5 x 10(-9) mol/L. The method was successfully applied to the determination of thiamine in pharmaceutical preparations.     

Indirect spectrophotometric determination of propranolol hydrochloride and piroxicam in pure and pharmaceutical formulations.

Two simple and sensitive indirect spectrophotometric methods for the assay of propranolol hydrochloride (PPH) and piroxicam (PX) in pure and pharmaceutical formulations have been proposed. The methods are based on the oxidation of PPH by a known excess of standard N-bromosuccinimide (NBS) and PX by ceric ammonium sulfate (CAS) in an acidic medium followed by the reaction of excess oxidant with promethazine hydrochloride (PMH) and methdilazine hydrochloride (MDH) to yield red-colored products. The absorbance values decreased linearly with increasing concentration of the drugs. The systems obeyed Beer's law over the concentration ranges of 0.5 - 12.5 and 0.3 - 16.0 microg/ml for PPH, and 0.4 - 7.5 and 0.2 - 10 microg/ml for PX with PMH and MDH, respectively. Molar absorptivity values, as calculated from Beer's law data, were found to be 1.36 x 10(4) and 2.55 x 10(4) l mol(-1) cm(-1) for PPH, and 2.08 x 10(4) and 2.05 x 10(4) l mol(-1) cm(-1) for PX with PMH and MDH, respectively. The common excipients and additives did not interfere with their determinations. The proposed methods have been successfully applied to the determinations of PPH and PX in various dosage forms. The results obtained by the proposed methods compare favorably with those of official methods.     

Flow-injection successive determination of cysteine and cystine in pharmaceutical preparations

A flow-injection configuration is proposed for the individual determination of cysteine and cystine and for the mixtures of both analytes. The procedure is based on the inhibitory effect of cysteine on the oxidation of thiamine to thiochrome by mercury(II). Linear calibration graphs were obtained between 1.0 x 10(-5) and 1.0 x 10(-4)M, with a sampling rate of 22 samples/hr and relative standard deviation of 1.14%. The inclusion of a selecting valve in the configuration, to pump water or hydroxylamine, allows the successive determination of these two analytes. The applicability of the method to the determination of cysteine and cystine in pharmaceutical preparations was demonstrated by investigating the effect of potential interferences and by the analysis of commercial preparations.     

Fluorimetric determination of peroxynitrite based on an enzymatic reaction.

A novel fluorimetric method for the determination of peroxynitrite (ONOO-) using hemoglobin (Hb) as a catalyst is described. The method employs the reaction of ONOO with thiamine (TM), a colorless, non-fluorescent reagent in a glycine-NaCl-NaOH buffer solution (pH 12.7), to generate a highly fluorescent product, thiochrome (TC). The fluorescent product was monitored by fluorimetry. A linear calibration graph was obtained over an ONOO- concentration range from 4.95 x 10(-7) mol L(-1) to 2.97 x 10(-5) mol L(-1), with a detection limit of 9.78 x 10(-9) mol L(-1) ONOO-. The relative standard deviation at an ONOO- concentration of 2.11 x 10(-6) mol L(-1) was 4.15% (n = 9).     

Utilization of 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) for kinetic spectrophotometric assay of befunolol hydrochloride in its pharmaceutical formulation

A simple, accurate, precise, and sensitive kinetic spectrophotometric method for determination of befunolol hydrochloride is described. The method is based on the formation of a colored product with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in methanol at 70 degrees C for 45 min. The red-colored product was measured at 523 nm. The optimization of various experimental conditions is described; Beer's law was obeyed in the range 15.25 x 10(-6) to 122.04 x 10(-6) M. The results obtained showed good recoveries (100.1 +/- 0.80%). Application of the proposed method to a pharmaceutical formulation was successfully achieved. The determination of befunolol hydrochloride by fixed time, fixed concentration, and rate constant methods was feasible with the calibration equation obtained. However, the fixed time method proved to be more applicable.     

Microsized graphite sensors for potentiometric determination of cyclobenzaprine hydrochloride in pure powder, tablets, and plasma

Two cyclobenzaprine hydrochloride (CZ) microsized graphite selective sensors were investigated with dibutylsebacate as a plasticizer in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) in the case of sensor 1, based on the interaction between the drug and the dissociated COOH groups in the PVC-COOH. Sensor 2 was based on the interaction between the drug and ammonium reineckate, which acted as anionic electroactive material in the presence of polyvinyl chloride matrix. The two sensors were constructed by using 2-hydroxy propyl beta-cyclodextrin as an ionophore, which has a significant influence on increasing the membrane sensitivity and selectivity of both sensors. Fast and stable Nernstian responses of 1 x 10(-5) - 1 x 10(-2) and 1 x 10(-4) - 1 x 10(-2) M for the two sensors, respectively, with slopes of 58.6 and 55.5 mV/decade, respectively, over the pH range 2-4 were obtained. The proposed method displayed useful analytical characteristics for determination of CZ in its pure powder form with average recoveries 99.95 +/- 0.23 and 99.61 +/- 0.34% for sensors 1 and 2, respectively, and in plasma with good recoveries. The sensors were also used to determine the intact drug in the presence of its degradate and, thus, could be used as stability-indicating methods. The obtained results by the proposed methods were statistically analyzed and compared with those obtained by the U.S. Pharmacopeia method; no significant difference for either accuracy or precision was observed. Results obtained with the two electrodes revealed their performance characteristics, which were evaluated according to International Union of Pure and Applied Chemistry recommendations.     

Potentiometric batch and flow injection analysis of betaine hydrochloride

Novel PVC membrane electrodes for the determination of betaine ion based on the formation of betaine-tetraphenylborate (Be-TPB) and betaine-phosphotungstate (Be-PT) ion-exchangers as electroactive materials are described. The sensors show a fast, stable, near Nernstian response for 6.92 x 10(-6) to 7.94 x 10(-3) M and 1.0 x 10(-4) to 1.0 x 10(-2) M betaine hydrochloride (Be.Cl) in case of Be-TPB electrode applying batch and flow injection analysis (FIA), respectively, and 2.95 x 10(-5) to 2.26 x 10(-3) M and 3.16 x 10(-5) to 1.0 x 10(-2) M in case of Be-PT electrode for batch and FIA electrodes, respectively, at 25 degrees C over the pH range of 3.5-10 with a cationic slope of 60.2 and 59.1 mV decade(-1) and a fast potential response of < or =15 s. The lower detection limits are 7.94 x 10(-6) and 3.18 x 10(-5) M Be.Cl for Be-TPB and Be-PT electrodes, respectively. Selectivity coefficient data for some common inorganic cations, sugars, amino acids and the components other than betaine, of the mixed drug investigated show negligible interference. The electrodes have been applied to the direct potentiometric determination of betaine hydrochloride in water and in a pharmaceutical preparation under batch and FIA conditions. Potentiometric titrations of Be.Cl with NaTPB and PTA as titrants were monitored with the developed betaine electrodes as an end point indicator electrode. The determination of Be.Cl shows an average recovery of 100.8% with mean relative standard deviation of 0.61%. The effect of temperature on the electrodes was also studied.     

Flow-injection chemiluminometric determination of some thioxanthene derivatives in pharmaceutical formulations and biological fluids using the [Ru(dipy)3(2+)]-Ce(IV) system.

A flow-injection (FI) methodology using tris(2,2'-dipyridyl)ruthenium(II), [Ru(dipy)3(2+)], chemiluminescence (CL) was developed for the rapid and sensitive determination of three thioxanthene derivatives, namely zuclopenthixol hydrochloride, flupentixol hydrochloride and thiothixene. The method is based on the CL reaction of the studied thioxanthenes with [Ru(dipy)3(2+)] and Ce(IV) in a sulfuric acid medium. Under the optimum conditions, calibration graphs were obtained over the concentration ranges 0.002-6 migrograms/ml for zuclopenthixol hydrochloride, 0.5-15 micrograms/ml for flupentixol hydrochloride and 0.05-7.5 micrograms/ml for thiothixene. The limits of detection (s/n = 3) were 4.2 x 10(-9) mol/l zuclopenthixol hydrochloride, 2 x 10(-8) mol/l flupentixol hydrochloride and 4.5 x 10(-8) mol/l thiothixene. The method was successfully applied to the determination of these compounds in dosage forms and biological fluids.     

Potentiometric membrane sensors for the selective determination of pyridoxine hydrochloride (vitamin B6) in some pharmaceutical formulations

The construction and general performance characteristics of two novel potentiometric PVC membrane sensors responsive to the pyridoxine hydrochloride known as vitamin B6 (VB6) are described. These sensors are based on the use of the ion-association complexes of the pyridoxine cation with phosphomolybdate, and phosphotungstate counter anions as ion pair in a plasticized PVC matrix. The electrodes show a stable, near-Nernstian response for 6x10(-5)-1x10(-2) M VB6 at 25 degrees C over the pH range 2-4 with a cationic slope of 54.0+/-0.5 and 54.5+/-0.4 per concentration decade for pyridoxine-phosphomolybdate and pyridoxine-phosphotungstate respectively. The two electrodes have the same lower detection limit (4x10(-5) M) and the response times are 45-60 and 30-45 s in the same order for both. Selectivity coefficients for VB6 relative to a number of interfering substances were investigated. There is negligible interference from many cations, some vitamins and pharmaceutical excipients. Direct potentiometric determination of 15-2000 microg/ml pyridoxine shows an average recovery of 98.0% and 99.0% with relative standard deviation 1.5% and 1.2% at 100.0 microg/ml for pyridoxine-phosphomolybdate and pyridoxine-phosphotungstate electrodes, respectively. The determination of VB6 in some pharmaceutical preparations using the proposed electrodes gave an average recovery of 98.0 and 99.0% of the nominal value and a mean standard deviation of 1.1% and 0.9% (n=10) for pyridoxine-phosphomolybdate and pyridoxine-phosphotungstate electrodes, respectively. The results compare favorably with data obtained by the British Pharmacopoeia method.     

Determination of trace procaine hydrochloride by differential pulse adsorptive stripping voltammetry with a Nafion modified glassy carbon electrode.

A sensitive and selective method for the determination of procaine hydrochloride with a Nafion-modified glassy carbon electrode has been developed. The voltammetric behavior of procaine hydrochloride on the Nafion-modified electrode indicated that the modified electrode not only increased the sensitivity of the determination of procaine hydrochloride, but also catalyzed the electrode process. Procaine hydrochloride was accumulated in Britton-Robinson buffer (pH 2.09) at a potential of -0.2 V (vs. SCE) for 180 s, and was then determined by differential pulse adsorptive stripping voltammetry. The effect of various parameters, such as the pH of the medium, the mass of drop-coated Nafion, the accumulation potential, the accumulation time and the scan rate, were investigated. Under the optimum conditions, a linear calibration graph was obtained in the concentration range of 6.0 x 10(-8) to 6.0 x 10(-6) mol l(-1) with a correlation coefficient of 0.9987. The relative standard deviation was 4.18% for eight successive determinations of 1.0 x 10(-7) mol l(-1) procaine hydrochloride, and the detection limit (three times signal to noise) was 7.0 x 10(-9) mol l(-1). A study of interfering substances was also performed, and the method was applied to the direct determinations of procaine hydrochloride in the injection solution of procaine hydrochloride and in rabbit serum.     

流动注射化学发光测定盐酸土霉素

水浴加热后的盐酸土霉素在磷酸介质中,过氧化氢存在下与高碘酸钠反应产生强烈的化学发光。结合流动注射技术建立了一种测定盐酸土霉纱的化学发光新方法。方法的线性范围为１．０＊１０＾－８－６．０＊１０＾－６ｇ／ｍＬ盐酸土霉素。检出限为４．３＊１０＾－９ｇ／ｍＬ,ＲＳＤ为２．５％（Ｃｓ＝２．０＊１０＾－６ｇ／ｍＬ;ｎ＝１１）。     

Determination of dissociation constants of cyclodextrin-ligand inclusion complexes by electrospray ionization mass spectrometry

The inclusion complexes of four ligands binding to cyclodextrins (CDs) were studied by electrospray ionization mass spectrometry (ESI-MS) and the dissociation constants of the complexes were obtained. The 1:1 stoichiometric inclusion complex was found in the system of CD and fenbufen or aspirin. The obtained KD values of the inclusion complexes of fenbufen binding to alpha-CD and to beta-CD are 4.38x10(-4) mol L(-1) and 2.12x10(-4) mol L(-1), respectively. The KD values of the inclusion complexes of alpha-CD-aspirin and beta-CD-aspirin are 3.33x10(-4) mol L(-1) and 1.83x10(-4) mol L(-1), respectively. A non-linear least squares regression method was applied to validate the results which were consistent with each other. For the system of tetracycline hydrochloride and CD, the 1:1 and 1:2 stoichiometric inclusion complexes were found in the mass spectra. The KD,1 and KD,2 values of the 1:1 and 1:2 stoichiometric inclusion complexes of alpha-CD and tetracycline hydrochloride are 4.47x10(-4) mol L(-1) and 6.51x10(-4) mol L(-1), respectively, and those of beta-CD and tetracycline hydrochloride are 2.26x10(-4) mol L(-1) and 8.57x10(-4) mol L(-1), respectively. For the system of norfloxacin and CD, besides the 1:1 and 1:2 inclusion complexes, the 1:3 stoichiometric inclusion complex was also found. The KD,1, KD,2 and KD,3 of alpha-CD and norfloxacin inclusion complexes are 4.61x10(-4) mol L(-1), 6.05x10(-4) mol L(-1) and 1.45x10(-3) mol L(-1), respectively. The three KD values of beta-CD and norfloxacin are 1.96x10(-4) mol L(-1), 4.93x10(-4) mol L(-1) and 1.15x10(-3) mol L(-1), respectively.     

Plastic membrane electrode for the potentiometric determination of pethidine hydrochloride in pharmaceutical preparations

A novel poly(vinyl chloride) membrane electrode with dibutyl phthalate as plasticizer based on the pethidine-tetraphenylborate ion-association complex as ion-exchange site for the determination of pethidine hydrochloride in injections and tablets was developed. A linear response for 1 x 10(-5) to 1 x 10(-2) mol/L drug with a slope of 51.77 mV/decade was established. The optimum pH range was 2-8. The lower detection limit was 2.18 x 10(-6) mol/L. There were negligible interferences from a number of inorganic and organic cations and some common drug excipients. The electrode proposed had been successfully applied to determine pethidine hydrochloride in tablets and injections. The results correlated well with those obtained by the United States Pharmacopoeia standard procedure.     

Enzymatic inhibition enthalpimetry: The analytical potential of the inhibitory action of a series of physiologically active alkaloids on the activity of serum cholinesterase

A kinetic method is described for the enthalpimetric determination of a series of physiologically active alkaloids based on their inhibitory effect on the cholinesterase-catalysed hydrolysis of butyrylcholine iodide. All analyses are done at pH 8.0 and at 25.0°C (short term stability ± 0.002°C). Precision (< 3.0%) data are reported for the determination of physostigmine sulphate (1.0–4.0 × 10^-8), quinine sulphate (1.0 × 10^-6–4.0 × 10^-5), procaine hydrochloride (1.0 × 10^-5–× 2.5 × 10^-4), atropine sulphate (5.0 × 10^-5–3.0 × 10^-4), morphine sulphate (1.0–8.0 × 10^-4), codeine phosphate (3.0 × 10^-4–2.4 × 10^-3), pilocarpine nitrate (5.0 × 10^-4––6.0 × 10^-3) and thiamine hydrochloride (1.0–5.0 × 10^-3); the linear response ranges in mol dm^-3 are given in parentheses. Complete inhibition curves are presented and relative “potency” is inferred. The effects of several interfering inhibitors are discussed.     

Papaverine PVC membrane ion-selective electrodes based on its ion-exchangers with tetraphenylborate and tetrathiocyanate anions

The construction and general performance of novel potentiometric membrane ion selective electrodes for determination of papaverine hydrochloride has been described. They are based on the formation of the ion association complexes of papaverine (PA) with tetraphenylborate (TPB)(I) or tetrathiocyanate (TTC)(II) counter anions as electro-active material dispersed in a PVC matrix. The electrodes show fast, stable, near Nernstian response for 1 x 10(-2) to 6 x 10(-5) M and 1 x 10(-2) to 1 x 10(-5) M for PA-TPB and PA-TTC respectively at 25 degrees C over the pH range of 3-5.0 with a cationic slope of approximately 56.5 +/- 0.5 mV/decade for both sensors respectively. The lower detection limit is 4 x 10(-5) and 8 x 10(-6) M for PA- I and PA-II respectively with fast response time ranging from 20-45 sec. Selectivity coefficients for PA relative to a number of interfering substances were investigated. There is a negligible interference from the studied cations, anions, and pharmaceutical excipients. The determination of 4.0- 3000.0 microg/ml of PA in aqueous solutions shows an average recovery of 99.1% and a mean relative standard deviation of 1.4 at 100microg/ml. The direct determination of PA in some formulations (Vasorin injection) gave results that compare favorably with those obtained using the British Pharmacopoeia method. Potentiometric titration of PA with sodium tetraphenylborate and potassium thiocyanate as titrants utilizing the papaverine electrode as an end point indicator electrode has been carried out.     

Determination of cimetidine,famotidine, and ranitidine hydrochloride in the presence of their sulfoxide derivatives in pure and dosage forms by high-performance thin-layer chromatography and scanning densitometry

A selective, precise, and accurate method was developed for the determination of cimetidine (C), famotidine (F), and ranitidine hydrochloride (R x HCl) in the presence of their sulfoxide derivatives. The method involves quantitative densitometric evaluation of mixtures of the drugs and their derivatives after separation by high-performance thin-layer chromatography on silica gel plates (10 x 20 cm) with ethyl acetate-isopropanol-20% ammonia (9 + 5 + 4, v/v) as the mobile phase for both C and F and ethyl acetate-methanol-20% ammonia (10 + 2 + 2, v/v) as the mobile phase for R x HCl; Rf values for C, F, and R x HCl and their corresponding derivatives were 0.85 and 0.59, 0.73 and 0.41, and 0.56 and 0.33, respectively. Developing time was approximately 20 min. For densitometric evaluation, peak areas were recorded at 218, 265, and 313 nm for C, F, and R x HCl, respectively. The relationship between concentration and the corresponding peak area was plotted for the ranges of 5-50 microg/spot for C and 2-20 microg/spot for F and R x HCl. Mean recoveries were 100.39 +/- 1.33, 99.77 +/- 1.30, and 100.09 +/- 0.69% for C, F, and R x HCl, respectively. The proposed method was used successfully for stability testing of the pure drugs in the presence of up to 90% of their degradates, in bulk powder and dosage forms. The results obtained were analyzed statistically and compared with those obtained by the official methods.