A Rapid Spectrophotometric Method to Resolve Ternary Mixtures of Propyphenazone, Caffeine, and Acetaminophen in Tablets

Summary.  A simple and rapid derivative spectrophotometric assay procedure is described for the analysis of caffeine (1), acetaminophen (2), and propyphenazone (3) in tablet formulations. The concentration range of application is 5.0–25.0 μg·cm⁻³ for 2 and 3 and 1.0–5.0 μg·cm⁻³ for 1. The method involves the extraction of the drugs from tablets with 0.1 N H₂SO₄, filtration, appropriate dilution, and measurement of the fourth derivative absorbance values at zero crossing wavelengths of 230.0, 263.2, and 256.6 nm for 1, 2, and 3. As a reference method, a reversed phase HPLC procedure was developed. Commercially available tablets were analyzed; statistical comparison of the results with those obtained from the reference method showed good agreement. The derivative spectrophotometric method has the advantage of being simple, rapid, inexpensive, and easy to perform. Received April 18, 2001. Accepted (revised) June 5, 2001     

A Rapid Spectrophotometric Method to Resolve Ternary Mixtures of Propyphenazone, Caffeine, and Acetaminophen in Tablets

 A simple and rapid derivative spectrophotometric assay procedure is described for the analysis of caffeine (1), acetaminophen (2), and propyphenazone (3) in tablet formulations. The concentration range of application is 5.0–25.0 μg·cm⁻³ for 2 and 3 and 1.0–5.0 μg·cm⁻³ for 1. The method involves the extraction of the drugs from tablets with 0.1 N H₂SO₄, filtration, appropriate dilution, and measurement of the fourth derivative absorbance values at zero crossing wavelengths of 230.0, 263.2, and 256.6 nm for 1, 2, and 3. As a reference method, a reversed phase HPLC procedure was developed. Commercially available tablets were analyzed; statistical comparison of the results with those obtained from the reference method showed good agreement. The derivative spectrophotometric method has the advantage of being simple, rapid, inexpensive, and easy to perform.     

Rotating barrier end groups in organic cumulenes

An elementary explanation in terms of MO theory is given for the stability of the various conformations of symmetry D _2h and D _2j for the organic cumulenes C_nH₄. Results are given for the rotation barriers for the end groups as derived by the restricted Hartree-Fock method in the semiempirical approximation for closed and open shells. It is found that the barrier is ~0.2 eV for an infinitely long cumulene with equal bonds. The origin of the effect is discussed, which is absent in the simple and extended forms of Hückel's method. It is shown that the ex-extended form of Hückel's method incorrectly gives barrier alternation.     

Development and validation of RP-HPLC method for simultaneous estimation of prednicarbate,mupirocin and ketoconazole in topical dosage forms

A simple and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for simultaneous estimation of prednicarbate (PC), mupirocin (MP) and ketoconazole (KT) in topical dosage forms. This combination is preferred for topical delivery of anti-inflammatory, antibacterial and antifungal agents for treatment of various skin disorders. The proposed RP-HPLC method utilizes a Hypersil GOLD C18, 5 μm, 250 mm × 4.6 mm i.d. column, mobile phase consisting of methanol-water (80: 20, v/v) adjusted to pH 5.0 with orthophosphoric acid in isocratic mode at the flow rate of 0.5 mL/min and UV detection at 243 nm. The method does not require any specific sample preparation except extraction of active pharmaceutical ingredients from the developed topical emulgel formulations using dichloromethane. Linearity was found in the range of 0.05–0.3 mg/L for PC and 0.4–2.4 mg/L for each of MP and KT with R ² > 0.999. The method is precise with low RSD%, accurate (overall average recovery yields: 99.92% for PC, 99.44% for MP and 99.74% for KT) and selective. Due to its simplicity and accuracy, the method is suitable for simultaneous analysis of PC, MP and KT in topical dosage forms.     

Spectrophotometric determination of methimazole,D-penicillamine,captopril, and disulfiram in pure form and drug formulations

A spectrophotometric method for the determination of methimazole (MT), D-penicillamine (PA), captopril (CA), and disulfiram (DM) was proposed. The method is based on the reaction of sulfur compound with N,N-dimethyl-p-phenylenediamine (DMPD) in acidic solution, in the presence of Fe³⁺ ions as oxidizing agent. The Beer’s law was obeyed in the range 16–110 mg of MT, 19–260 mg of PA, 29–160 mg of CA, and 36–110 mg of DM. The method was successfully applied to the quantification of these compounds in pharmaceuticals.     

Simple UV and visible spectrophotometric methods for the determination of doxycycline hyclate in pharmaceuticals

Doxycycline hyclate (DOX), a broad spectrum antibiotic with activity against a wide range of gram-positive and gram-negative bacteria, is widely used as a pharmacological agent and as an effector molecule in inducible gene expression system. Three simple, selective, rapid, accurate, precise and cost-effective spectrophotometric methods for the determination of DOX in bulk drug and in tablets have been developed and validated. First method (method A) is based on the measurement of absorbance of DOX in 0.1 M HCl at 240 nm. The second method (method B) is based on the measurement of yellow chromogen at 375 nm which is formed in 0.1 M NaOH. The third method is based on the measurement of 2: 1 complex formed between DOX and iron(III) in H₂SO₄ medium, the complex peaking at 420 nm (method C). The optimum conditions for all the three methods are optimized. Beer’s law was obeyed over the ranges 2.5–50.0, 1.50–30.0 and 10–100 g/mL for method A, method B and method C, respectively. The apparent molar absorptivity values are calculated to be 1.03 × 10⁴, 1.73 × 10⁴, and 5.21 × 10³ L mol⁻¹ cm⁻¹ for method A, method B, and method C, respectively. The Sandell sensitivity, limit of detection (LOD) and limit quantification (LOQ) values are also reported. All the methods were validated in accordance with current ICH guidelines. The developed methods were employed with high degree of precision and accuracy for the estimation of total drug content in commercial tablet formulations of DOX.     

Potentiometric Determination of Potassium in Seawater and Interstitial Water

Abstract

A method is described for the determination of potassium in seawater and marine sediment porewater. After precipitation of the halogen ions with AgNO₃, potassium is precipitated with sodium tetraphenylborate. The excess tetraphenylborate is then determined by AgNO₃ titration, using a silver electrode for end-point detection. Application of this method to seawater samples as small as 1 cm³, gave accuracy and precision of better than 1%.     

Prediction of rizatriptan trace level in biological samples: An application of the adaptive-network-based fuzzy inference system (ANFIS) in assisting drug dose monitoring

Introduction: Solvent bar microextraction technique is a sample preparation method prior to analysis for complicated matrices such as urine, blood, stem cell culture, and wastewater. This method, when coupled with adaptive-network-based fuzzy inference system, can detect and predict the concentration of trace elements and drugs at ultra-trace levels in complicated matrices.

Material and method: Rizatriptan was used as a model drug for validation of this method. Therefore, six parameters (pH of donor and acceptor phase, stirring rate, time, temperature, and salt addition) affecting the preconcentration and determination of this drug were investigated. In this method, pH gradient was applied to transfer the drug into the solvent bar. MATLAB version 2010 was used for data analysis. Construction of an input-output mapping was done based on the results obtained from the experiments. For the simulation, the ANFIS architecture was employed to model nonlinear functions, identify nonlinear components in a control system, and predict a chaotic time series, all yielding remarkable results. Based on the best model chosen, the drug was preconcentrated and analyzed under the optimum condition.

Results and discussion: The figures of merit were as follows: preconcentration factor: 127; limit of detection: 15?ng?mL^?1; limit of quantification: 50?ng?mL^?1; R²:0.999; RSD: 3.0%(interday) and 4.6% interaday. As a result, this method can be employed for preconcentration and microextraction of several elements, drugs, antibodies at trace levels in complicated matrices. After modeling, the optimum condition could be predicted without performing unnecessary and expensive experiments.

Conclusion: Certain biomarkers can also be preconcentrated and detected using the proposed method. It offers high sample clean up, therefore it can be used for clean validation. Prediction of the course of treatment may be possible with the proposed method, therefore it is highly practical, easy and cost-effective.     

Stability Indicating Hplc Method for the Determination of Sparfloxacin (Spar)

ABSTRACT

A rapid, sensitive and stability indicating method for the determination of sparfloxacin (SPAR) by RP - HPLC has been developed on a Merck RP - Select B (5 μm; 12.5 cm x 4.0 mm) column using a mobile phase of water: acetonitrile: triethylamine (80 : 20 : 0.2 v/v) pH of which was adjusted to 2.6 with orthrophosphoric acid. The flow rate was 1 ml / min. and the detection was carried out at 304 nm using Waters 486 variable wavelength detector. The retention time for SPAR was 7.2 min. Linearity range was from 8 - 1000 ppm. The method showed good precision and accuracy when applied to two brands of tablets containing SPAR. In alkaline media SPAR is stable where as it undergoes degradation in acidic and oxidising conditions generating different degradation products the nature of which is required to be established. The proposed method nicely separates the degraded products from SPAR and hence can be used as stability indicating method for the assay of SPAR.     

O-H bond dissociation energies in hydroquinones and 4-hydroxyphenoxyl radicals and effect of solvation on the kinetics of reactions involving hydroquinones and semiquinone radicals

The O-H bond dissociation energies (D _OH) in the molecules of 2,5-dimethylhydroquinone (1) and 2,5-di-tert-butylhydroquinone (2) and in the corresponding semiquinone radicals (5 and 8, respectively) were estimated by the method of intersecting parabolas (IP) from experimental data on the rate constants for the reactions of these compounds with N-phenyl-1,4-benzoquinonemonoimine (3) and using the density functional B3LYP/6-31+G* quantum chemical calculations. When calculating the D _OH values by the IP method, solvation of reactants and transition states should be taken into account. The energies of solvation of quinones, semiquinone radicals, and hydroquinones were evaluated by the PCM method. The results of quantum chemical calculations obtained with inclusion of the effects of solvation and the D _OH estimates obtained by the IP method are in good agreement, being equal to 337.9±1.6, 242.5±1.4, and 242.7±3.4 kJ mol⁻¹ for molecule 1 and radicals 5 and 8, respectively. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2244–2251, October, 2005.     

Development of spectrofluorimetric methods for the determination of levosulpiride in pharmaceutical formulation

Simple, accurate, rapid, and sensitive spectrofluorimetric methods for the determination of levosulpiride in pharmaceutical formulation were developed utilizing its fluorescence reaction with Fe³⁺ (method A) and Al³⁺ (method B). The calibration curves were found to be linear in the concentration range 0.239–3.44 μg/mL and 0.310–2.730 μg/mL with limit of detection 0.005 μg/mL and 0.0032 μg/mL, respectively, for method A and method B. The reaction conditions were studied and optimized. In addition, the complexation of Mg²⁺ and Ca²⁺ was also studied. In all cases, an enhancement in fluorescence emission of levosulpiride upon formation of complex with metal ions was observed. A 2: 1 (drug: metal) stoichiometry for all the complexes was established. Benesi-Hildebrand method was applied for calculation of association constant at 25 and 35°C. The thermodynamic parameters obtained in this study revealed that the interaction process was spontaneous and mainly ΔS-driven.     

Stability-indicating high performance thin layer chromatographic determination of sulfanilamide in human urine

A simple, sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method was developed and applied to human urine for the densitometric determination of sulfanilamide. A mixture of chloroform-ethyl acetate-xylene (2.5: 4.0: 1.0, v/v/v) was used as a mobile phase. The system was found to give compact spots for sulfanilamide (retardation factor, R _f = 0.21±0.02). The linear regression analysis data for the calibration plots showed good linear relationship with r ² = 0.9970 ± 0.0003 and r ² = 0.9947 ± 0.020 within the concentration range of 50–250 ng per spot and 100–1000 ng per spot with respect to peak area, respectively. The limit of detection (LOD) and quantification (LOQ) were 8 and 25 ng per spot, respectively. Sulfanilamide was subjected to acid and alkali hydrolysis, oxidation, dry heat and wet heat treatment. According to the International Conference on Harmonization (ICH) guidelines the method was validated for precision, recovery and robustness. The ultraviolet (UV) spectra of the degradation products which had different spectra from sulfanilamide were also recorded. The article is published in the original.     

A NEW APPROACH TO ISOLEVOGLUCOSENONE VIA THE 2,3-SIGMATROPIC REARRANGEMENT OF AN ALLYLIC SELENIDE

A convenient method is described for the synthesis of isolevoglucosenone 5, via allylic selenide 3, and its rearrangement to allylic alcohol 4, followed by oxidation with manganese oxide. Isolevoglucosenone 5, is produced in 62% overall yield.     

The HPLC Analysis of Caffeine and Theobromine in Animal Diets

Abstract

An HPLC method is described for the analysis of added caffeine and theobromine in animal diets using HPLC with samples extracted in CHC1₃ and interferences eliminated with a Sep-pak^tm. This method has good accuracy and precision but is not suitable for matrixes where the methylxanthines exist as a integral part of the matrix (e.g., foods).     

Accuracy in the Determination of Recovery in HPLC

Abstract

A method for the determination of the recovery in RP-HPLC using fluorescence and UV-detection is presented and compared with radioisotope experiments. A sensitive and specific detection is necessary in order to obtain accurate results.     

High-Performance Liquid Chromatographic Determination in Human Plasma of a Anticonvulsant Benzodiazepine: Clonazepam

Abstract

A rapid and specific high-pressure liquid chromatography method for determination of clonazepam in human plasma is described.

The analysis is linear for concentrations ranging from 5 to 100 ng. ml^-1 plasma for clonazepam.

The method is applicable to quantitation of clonazepam in human plasma of subjects receiving 0.05 at 0.20 mg.kg^-1 orally, with satisfactory accuracy and precision.     

HPLC simultaneous determination of arbutin,chlorogenic acid and 6′-O-caffeoylarbutin in different parts of Vaccinium dunalianum Wight

Arbutin (1), chlorogenic acid (2) and 6′-O-caffeoylarbutin (3) are three major components in Vaccinium dunalianum Wight with various promising bioactivities. A reliable, reproducible and accurate method for simultaneous and quantitative determination of 1–3 is developed by RP-HPLC analysis. This method should be appropriate for the quality assurance of unprocessed and processed materials of V. dunalianum. The contents of 1–3 in different parts of V. dunalianum from different origins were analysed. The content of 3 was much higher than those of 1 and 2, accounting for up to 31.76% in the dried leaf buds. Moreover, the leaf buds, flower buds and leaves showed a tendency towards higher contents of 1–3 than the other plant parts.     

Efficient Synthesis of 2‐Aminothiazole‐4‐phenyl‐5‐acetamides via the Open Chain Tautomers of γ‐Keto Amides

A simple and efficient method is described for the synthesis of new functionalized 2‐aminothiazoles, the 2‐aminothiazole‐4‐phenyl‐5‐acetamides 5, in 67–96% yields based on an application of the Hantzsch synthesis. The method involves the reaction of thiourea with 3‐benzoyl‐3‐bromo‐propionamides 4 prepared from the corresponding 3‐benzoylpropionamides 3. The tautomeric structure of the γ‐keto amides 3 and 6 is directly related to the present study, because 2‐aminothiazoles 5 are readily obtained from the corresponding open chain γ‐keto amides 3.     

Simultaneous Determination of Andrographolide and Dehydroandrographolide in Chicken Plasma for Application to Pharmacokinetic Studies

A simple, suitable reverse phase liquid chromatographic method was developed for simultaneous determination of andrographolide (1) and dehydroandrographolide (2) in chicken plasma after orally administrating the ultra-fine powder of Andrographis paniculata. Plasma samples were extracted with ethyl acetate. Analysis of the extract was performed on a reversed-phase C18 column with gradient eluent composed of acetonitrile and 0.5% acetic acid. The flow rate was kept at 1 mL min⁻¹ and the detection wavelength was set at 225 and 255 nm for 1 and 2, respectively. All calibration curves showed good linear regression (R ≥ 0.9991). The good precision and recoveries with intra-day and inter-day were 3.2–8.7% and 91.1–98.4%, respectively. The limit of detection was 0.016 µg mL⁻¹ and the limit of quantitation was 0.040 µg mL⁻¹ for the target analytes. This validated method has been successfully applied in the pharmacokinetics study of 1 and 2 after orally administrating the Andrographis paniculata ultra-fine powder to chicken.