Determination of volatile residual solvents in pharmaceutical products by headspace liquid-phase microextraction gas chromatography-flame ionization detector

This paper demonstrates headspace liquid-phase microextraction (HS-LPME) as used for the determination of volatile residual solvents in pharmaceutical products. This method is based on headspace liquid-phase microextraction capillary column gas chromatography. Under optimum conditions, the linerary of the method ranged from 1 to 1,000 mg l⁻¹. The limits of detection are 0.2–2.0 mg l⁻¹ and relative standard deviations (RSD) for most of the volatile solvents were below 10%. This novel method is applied to the analysis of volatile residual solvents in pharmaceutical products with satisfactory results.     

A review on speciation of iodine-129 in the environmental and biological samples

As a long-lived beta-emitting radioisotope of iodine, ¹²⁹I is produced both naturally and as a result of human nuclear activities. At present time, the main part of ¹²⁹I in the environment originates from the human nuclear activity, especially the releases from the spent nuclear fuel reprocessing plants, the ¹²⁹I/¹²⁷I ratios have being reached to values of 10⁻¹⁰ to 10⁻⁴ in the environment from 10⁻¹² in the pre-nuclear era. In this article, we review the occurrence, sources, inventory, and concentration level of ¹²⁹I in environment and the method for speciation analysis of ¹²⁹I in the environment. Measurement techniques for the determination of ¹²⁹I are presented and compared. An overview of applications of ¹²⁹I speciation in various scientific disciplines such as radiation protection, waste depository, and environmental sciences is given. In addition, the bioavailability and radiation toxicity (dose to thyroid) of ¹²⁹I are discussed.     

A rapid and highly sensitive stability-indicating high-performance thin-layer chromatography technique for the determination of tedizolid phosphate with a classical univariate calibration

No high-performance thin-layer chromatography (HPTLC) techniques have been established for the determination of tedizolid phosphate (TDZP) in pharmaceutical products or physiological fluids. Therefore, a rapid and highly sensitive stability-indicating HPTLC technique has been developed for the determination of TDZP in commercial formulations with a classical univariate calibration. The HPTLC‒densitometry analysis of TDZP was carried out via chloroform‒methanol (90:10, V/V) mobile phase. The determination of TDZP was performed at the wavelength of 300 nm. The proposed HPTLC technique was linear in the range of 10‒2000 ng band^‒1. In addition, the method was found to be highly accurate (% recovery = 98.53‒101.74%), precise (%CV = 0.67‒0.91%), robust (%CV = 0.83‒0.86%), highly sensitive (LOD = 3.41 ng band^‒1, LOQ = 10.23 ng band^‒1) for the determination of TDZP. The proposed technique was also able to detect TDZP in the presence of its degradation products under various stress conditions and it can be considered as a stability-indicating method. The proposed HPTLC technique was applied for the analysis of TDZP in its commercial formulations. The TDZP contents of commercial tablets and injection were determined as 98.41% and 101.23%, respectively. These results suggested that the proposed HPTLC technique can be applied for the routine analysis of TDZP in its commercial products and newly established formulations.

     

A spectrophotometric method for quantitative determination of lactulose in pharmaceutical preparations

A simple spectrophotometric assay for the quantification of lactulose in pharmaceutical preparations was developed. The method is based on hydrolysis of lactulose under acidic conditions. The hydrolyzed product reacts with resorcinol, giving absorption peaks at 398 and 480 nm. Both absorption wavelengths can be used for the determination of lactulose. The limit of detection of lactulose at 398 nm and 480 nm was 0.075 μg mL⁻¹ and 0.65 μg mL⁻¹, respectively. The calibration was linear in the range of 5–25 μg mL⁻¹. Analytical conditions were optimized, and the method was validated for analysis of pharmaceutical preparations. The determined amount of lactulose was found to be in good agreement with labeled claims in commercial products. The proposed method is economical, convenient, and suitable for the quantification of lactulose in pharmaceutical preparations. The text was submitted by the authors in English.     

TLC Determination of Amitriptyline HCl,Trifluoperazine HCl,Risperidone and Alprazolam in Pharmaceutical Products

A simple, sensitive, and precise thin layer chromatographic (TLC) method for simultaneous analysis of psychopharmacological drugs like amitriptyline HCl, trifluoperazine HCl, risperidone and alprazolam in their single dosage forms has been developed, validated, and used for determination of the compounds in commercial pharmaceutical products. The TLC separation was carried out on Merck TLC aluminium sheets of silica gel 60 F254 using carbon tetrachloride:acetone:triethylamine (8:2:0.3, v/v/v), as mobile phase. Densitometric measurements of their spots were achieved at 250 nm over the concentration range for amitriptyline HCl (50–1,200 ng spot⁻¹), trifluoperazine HCl (50–1,200 ng spot⁻¹), risperidone (100–2,400 ng spot⁻¹) and alprazolam (25–600 ng spot⁻¹). Limit of detection (LOD) for amitriptyline HCl (20 ng spot⁻¹), trifluoperazine HCl (20 ng spot⁻¹), risperidone (40 ng spot⁻¹) and alprazolam (5 ng spot⁻¹) was obtained. The study showed that TLC was sensitive and selective for determination of amitriptyline HCl, trifluoperazine HCl, risperidone and alprazolam using a single mobile phase. This proposed method is able for simultaneous determination of psychopharmacological drugs and also applicable for analysis of pharmaceutical formulations.

     

Spectrophotometric Determination of Selected Antibiotics Using Prussian Blue Reaction

A simple, sensitive and accurate spectrophotometric method has been described for the determination of ampicillin(I), amoxicillin trihydrate(II) and cefazolin sodium(III). The procedure is based on the formation of Prussian Blue (PB) complex. The reaction between the acidic hydrolysis products of antibiotics (T = 60 °C) with mixture of Fe³⁺ and hexacyanoferrate(III) ions was evaluated for the spectrophotometric determination of the mentioned drugs. The maximum absorbance of the colored complex occurs at λ = 700 nm and the molar absorptivity is 3.0 × 10⁴ 1 mol^?1cm^?1. The effect of various parameters such as concentration of K₃Fe(CN)₆ and Fe³⁺, nature and amount of acids used, temperature and time of heating were investigated. Under optimum conditions the linear range of calibration graph was 2.0–12.0, 5.0–13.5 and 3.0–12.0 μg mL^?1 for ampicillin, amoxicillin and cefazolin, respectively. The relative standard deviation for the determination of 10 μg mL^?1 of antibiotics was about 0.5–1.5%. The proposed method was successfully applied to the determination of selected antibiotics from pharmaceutical preparations. The validity of the method was tested by the official methods and by the recovery studies of standard addition to pharmaceuticals.     

Development and Validation Method for Silica Determination by Spectrophotometry in Some Herbs and Pharmaceutical Formulations

ABSTRACT

A spectrophotometric method for determination of silica in herbs and herbal pharmaceutical products has been developed and validated. The method showed excellent accuracy and precision with S.D. 1.67 and RSD 1.72%, 2.75%, respectively. The established linearity range was 0.05–0.5 μg/mL(r² > 0.99974). The recovery of silica from spiked placebo was > 95% over the linear range. The method has been successfully used in the analysis of silica in raw material and herbal pharmaceutical formulations. This validated method proved to be rapid and less costly.     

Sequential injection method for the direct spectrophotometric determination of bismuth in pharmaceutical products

A spectrophotometric method is reported for the determination of bismuth in pharmaceutical products using sequential injection analysis. Methylthymol blue (MTB) was used as a color forming reagent and the absorbance of the Bi(III)-MTB complex was monitored at 548 nm. The various chemical and physical variables that affected the reaction were studied. A linear calibration graph was obtained in the range 0.0-75.0 mg l⁻¹ Bi(III) at a sampling frequency of 72 h⁻¹. The reagent consumption was considerably reduced compared to conventional flow injection systems, as only 150 μl of MTB were consumed per run. The precision was very satisfactory (s_r=0.5%, at 50.0 mg l⁻¹ Bi(III), n=12) and the limit of detection, c_L, was 0.250 mg l⁻¹. The developed method was applied successfully to the analysis of various pharmaceutical products containing Bi(III). The relative errors e_r, were <1.5% in all cases and were evaluated by comparison of the obtained results with those found using atomic absorption spectrometry as the reference method.     

Current status and future plan for the production of radioisotopes using HANARO Research Reactor

The Korea Atomic Energy Research Institute (KAERI) completed the High-flux Advanced Neutron Application Reactor (HANARO) in 1995 and the radioisotope production facilities(RIPF) in 1997. Many devices and handling tools were developed and applied for the production of radioisotopes. Emphasis on RI production plan was placed on the development of new radiopharmaceuticals, the development of new radiation sources for industrial use and the steady production of selected radioisotopes. The selected items are ¹⁶⁶Ho-based pharmaceuticals, fission ⁹⁹Mo/^99mTc generators, and products of ¹³¹I and ¹⁹²Ir and ⁶⁰Co sources for industrial use. Now KAERI regularly produces radioisotopes (¹³¹I, ^99mTc, ¹⁶⁶Ho, ¹⁹²Ir, ⁶⁰Co etc.) and labeled compounds including ^99mTc cold kits. Newly developed therapeutic agents are a ¹⁶⁶Ho-chitosan complex for liver cancer treatment, a ¹⁶⁶Ho patch for skin cancer treatment and devices such as the stent and balloon for the prevention against restenosis of the coronary artery. Feasibility studies on the installation of a ^99mTc generator loading facility and on ⁶⁰Co production for food irradiation were finished. The ¹⁹²Ir sealed source assembly for NDT has been supplied to domestic users since May 2001. The fission moly process, separation process of non-sealed sources (¹²⁵I, ³³P, ⁸⁹Sr, ¹⁵³Sm, ¹⁸⁸Re) and fabrication process of sealed sources (¹⁶⁹Yb, ⁷⁵Se) are also under development. For the quality assurance of our final products, we obtained ISO certification in 2000. We are carrying out a feasibility study on a new research reactor for the stable supply of radioisotopes in Korea.     

Colorimetric Determination of Ampicillin and 6-Aminopenicillanic Acid Using Acenaphthenequinone as a Chromophoric Reagent

Abstract

A colorimetric method for the determination of ampicillin (Amp.) and 6-aminopenicillanic acid (6-APA) are described, based on the reaction of these drugs with acenaphthenequinone in basic media to give a highly intense red coloured product. The latter exhibits an absorption maximum at 610 nm with apparent molar absorptivities of 2.83 and 1.45 × 10⁴ l. mol^?1 cm^?1 and Sandell sensitivities of 0.013 and 0.015 μg cm^?2 for Amp. and 6-APA, respectively. The optimum concentration ranges are 0.4-10 and 0.4-14 μg ml^?1 for Amp. and 6-APA, respectively. For more accurate results, Ringbom optimum concentration ranges are 1–8.5 and 1–12 μg ml^?1 for Amp. and 6-APA, respectively. Statistical analysis indicated that there was no significant difference between the results obtained by the described method and those of the official methods. The mean recoveries percentage were found to be 99.5 × 1.1% for pharmaceutical formulations and 99.1 × 1.6% for serum and urine samples. The method is selective for the determination of Amp. or 6-APA in the presence of their degradation products, additives and excipiences that are normally encountered in dosage forms. The proposed method was applied successfully to the determination of Amp. in pharmaceutical formulations. Also, applicability of the proposed method to human serum and urine is presented and the validity assessed by applying the standard addition technique.     

A Potentiometric Sensor for Determination of Doxycycline Hydrochloride in Pharmaceutical Preparation and Biological Fluids

This article focused on the construction and characteristics of novelty and sensitivity of modified carbon paste electrodes for determination of doxycycline hydrochloride (DC.HCl) in urine, serum and pharmaceutical preparations. It was based on the incorporation of α-cyclodextrine (α-CD) and multi-walled carbon nanotube (MWCNT) ionophores which improved the characteristics of the electrodes with tricresylphosphate (TCP) (electrode I) and o-nitrophenyloctylether (o-NPOE) (electrode II) as plasticizers, respectively. The constructed electrodes, at optimum paste composition, exhibited good Nernstian response for determination of doxycycline hydrochloride over a linear concentration range from 1.0 × 10^–7 to 1.0 × 10^–2 and 1.22 × 10^–7 to 1.0 × 10^–2 mol L^–1 with detection limit of 1.0 × 10–7 and 1.22 ×10^–7 mol L^–1 and with slope values of (58.7 ± 0.2) mV decade–1 and (58.0 ± 0.6) mV decade–1, for modified carbon paste electrodes (MCPEs; electrodes I and II), respectively. The results showed fast dynamic response time (about 6–7 s) and long lifetime in the range from 4 to 5 months where the response of the electrodes was not affected by pH variation within the range from 2 to 8 and 2 to 7.5 for electrodes I and II, respectively. Electrodes I and II showed high selectivity for doxycycline hydrochloride with respect to a large number of interfering species including foreign inorganic, organic species, excipients and the fillers added to the pharmaceutical preparation. The constructed electrodes were successfully applied for determination of DC.HCl in pure form, its pharmaceutical preparations and biological fluids (urine and serum) using standard addition, calibration curves and potentiometric titration methods. The results obtained using these potentiometric electrodes were comparable with those obtained using official method. The results were satisfactory with excellent percentage recovery comparable or better than those obtained by other routine methods.

     

Determination of water-soluble vitamins in pharmaceutical preparations by reversed-phase high-performance liquid chromatography with a mobile phase containing sodium dodecylsulphate andn-propanol

Summary A reversed-phase liquid chromatographic method with sodium dodecylsulphate-n-propanolwater as mobile phase has been used to separate and determine six water-soluble vitamins in twelve minutes. The analytical characteristics linear range, sensitivity, detection limits, and precision were evaluated. The lowest detection limits were those of nicotinic acid (not usually present in pharmaceutical products), 0.7 mgL⁻¹, nicotinamide, 1.3 mg L⁻¹, and pyridoxine, 1.4 mg L⁻¹. When the method was applied to the determination of the vitamins in pharmaceutical samples the values found agreed with those on the labels.     

Can a radioactive implant induced X-ray emission (RIXE) technique be used to in vivo measurement of heavy elements?

A radioactive implant induced X-ray emission (RIXE) technique was examined for the in vivo determination of heavy elements. By the use of⁶⁷Ga,^99mTc,¹²³I,¹²³Xe and²⁰¹Tl implant excitation sources, the excitation efficiency and X-ray attenuation were measured to reveal the potential pairs of source-heavy element of interest for in vivo elemental analysis by the RIXE technique. Detection limits for the RIXE in vivo analysis were evaluated according to Currie's criterion. Four pairs,^99mTc–Pb,²⁰¹Tl–I,¹³³Xe–Cd and¹²³I–Cd are potential.     

Simultaneous determination of bifonazole and tinctures of calendula flower in pharmaceutical creams by reversed-phase liquid chromatography

The aim of this research was to develop and validate a sensitive, rapid, easy, and precise reversed-phase liquid chromatography (LC) method for stability studies of bifonazole (I) formulated with tinctures of calendula flower (II). The method was especially developed for the analysis and quantitative determination of I and II in pure and combined forms in cream pharmaceutical formulations without using gradient elution and at room temperature. The influence on the stability of compound I of temperature, artificial radiation, and drug II used for the new pharmaceutical design was evaluated. The LC separation was carried out using a Supelcosil LC-18 column (25 cm x 4.6 mm id, 5 microm particle size); the mobile phase was composed of methanol-0.1 M ammonium acetate buffer (85 + 15, v/v) pumped isocratically at a flow rate of 1 mL/min; and ultraviolet detection was at 254 nm. The analysis time was less than 10 min. Calibration graphs were found to be linear in the 0.125-0.375 mg/mL (rI = 0.9991) and 0.639-1.916 mg/mL (rII = 0.9995) ranges for I and II, respectively. The linearity, precision, recovery, and limits of detection and quantification were satisfactory for I and II. The results obtained suggested that the developed LC method is selective and specific for the analysis of I and II in pharmaceutical products, and that it can be applied to stability studies.     

Electrochemical Determination of Vitamin D3 in Pharmaceutical Products by Using Boron Doped Diamond Electrode

A sensitive square‐wave voltammetry method was developed to determine cholecalciferol (vitamin D₃) in pharmaceutical products at boron‐doped diamond electrode as a working electrode. Vitamin D₃ provided a well‐defined voltammetric peak at around +1.00 V (vs. Ag/AgCl, 3.5 mol dm^?3) in 0.02 mol dm^?3 Britton‐Robinson buffer pH 5.0 prepared in 50 % ethanol. The influence of various factors such as type and pH of the supporting electrolyte, scan rate and square‐wave parameters were studied and optimized. Under optimum conditions, the oxidation peak current increased linearly with the concentration of vitamin D₃ over the range of 2 to 200 μmol dm^?3. The calculated limit of detection and limit of quantitation were 0.17 μmol dm^?3 and 0.51 μmol dm^?3, respectively. The boron‐doped diamond electrode exhibited specific recognition capability for cholecalciferol amongst possible interferences, and the determination of vitamin D₃ was possible in samples such as commercial pharmaceutical products without complicated sample pretreatments.     

Quantification of erythromycin in pharmaceutical formulation by transmission Fourier transform infrared spectroscopy

A simple, cost-effective and environmental friendly analytical method was developed for the quantification of erythromycin in tablet formulation using transmission Fourier Transform Infrared (FT-IR) spectroscopy for routine quality control analysis. There is no need of sample preparation except pellet formation for FT-IR analysis. Use of solvent was totally avoided in this method. Calibration was carried out by using simple Beer’s law in the FT-IR region between 1743 and 1697 cm⁻¹. The excellent coefficient of determination (R² = 0.998) was achieved with 0.0247 and 1.14 root mean square error of prediction (RMSEP) and root mean square error of cross validation (RMSECV), respectively. The results of the study revealed that the transmission FT-IR spectroscopy could be effectively used for rapid determination of active ingredients like erythromycin in pharmaceutical formulations to control the quality of finished products.     

Development and Validation of a Stability Indicating LC Method for the Determination of Faropenem in Pharmaceutical Formulations

A simple, selective and sensitive stability indicating LC method has been developed and validated for the determination of faropenem in bulk drug and pharmaceutical formulations in the presence of degradation products. The separation was achieved by using an isocratic mobile phase mixture of acetate buffer of pH 3.5 and methanol (65:35, v/v) and 250 mm × 4.6 mm I.D., 5 μm particle size SGE make Wakosil C-18 AR column at flow rate of 1.0 mL min^?1 with detection at 305 nm. The retention time of faropenem is 6.63 min and was linear in the range of 5–75 μg mL^?1 (r = 0.9999). The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation and was found to be unstable in all the stress conditions. The proposed method was successfully employed for quantification of faropenem in bulk drug and its pharmaceutical formulations.     

Batch Injection Analysis Utilizing Modified Electrodes with Tetraruthenated Porphyrin Films for Acetaminophen Quantification

Batch injection analysis (BIA) utilizing amperometric detection with glassy carbon electrodes modified with [Co(TPyP){Ru(bipy)₂Cl}₄](TFMS)₅?H₂O porphyrin films were explored for acetaminophen analysis in pharmaceutical formulations. BIA is an interesting alternative for application of electrodes modified with tetraruthenated porphyrins. This sensor exhibited sharp current response peaks, rapid washout and excellent reproducibility for BIA‐amperometric quantification of acetaminophen. Also, a wide linear working range (10^?4 to 10^?6 mol L^?1) as well as high sensitivity and sampling frequency rate (detection limit=1.1×10^?7 mol L^?1, sampling frequency=120 injections/h) and a small volume of analysis (100 μL/injection) was achieved. Furthermore, the proposed method permits the direct quantification of acetaminophen in many pharmaceutical products, avoiding cumbersome processes as previous separations, solvent extraction or sample filtration. The new procedure was applied to the analysis of commercial pharmaceutical products and the results were in excellent agreement with the ones obtained by spectrophotometric method. Accordingly, this amperometric method showed to be very well suited for quality control analysis and other applications with similar requirements.     

Determination of the specific activity of carrier-free125I preparations by neutron activation analysis

Chemical methods are unsuitable for the determination of the specific activity of commerical¹²⁵I preparations because of the unknown chemical state of the iodine in solutions more than a few weeks old.¹²⁵I and¹²⁷I were determined in samples from seven different manufacturers by instrumental neutron activation analysis; the specific activities found ranged from about 45% to more than 90% of that of the truly carrierfree product. Correlation of the specific activities with the¹²⁶I:¹²⁵I ratios indicates contamination of one of the products with stable iodine during the manufacturing process. Part of this paper was presented at the 1968 Internat. Conf. on Modern Trends in Activation Analysis.     

LC Method for Studies on the Stability of Sibutramine in Soft Gelatin Capsules

A sensitive and rapid liquid chromatographic method was successfully developed and validated for the determination of sibutramine hydrochloride in bulk and capsules. Sibutramine in the presence of its degradation products was analyzed using UV detection at 225 nm. Chromatography was performed on a reversed-phase C₈ (150 × 4.0 mm I.D., 5 μm) analytical column under isocratic conditions. The mobile phase was composed of acetonitrile:water (aqueous phase containing 0.3% triethylamine and pH adjusted to 7.0) (75:25, v/v) at a flow-rate of 1.1 mL min⁻¹. No chromatographic interference was found during the analysis. Light was the stress condition which most contributed to sibutramine degradation. The method showed a linear response (r > 0.999) from 30 to 90 μg mL⁻¹. The mean recovery for capsules was 101.2%. Inter-day assays showed relative standard deviations of 0.42 and 1.62% for bulk and capsules, respectively. The developed method is able to separate sibutramine from its major degradation products and it may be used in the quality control of this active pharmaceutical ingredient in both bulk and capsules.