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Background: Amikacin sulfate (AMK) belongs to the class of aminoglycoside antibiotics. It is effective against the infections caused by Gram-negative and positive bacteria. AMK lacks a chromophore group in its structure and, therefore, it does not absorb light in the 200-800 nm region which makes it a difficult molecule to analyze by UV detector using high performance liquid chromatography (HPLC). Objective: This study has been carried out to develop and validate a relatively simple, accurate, precise, rapid, economical, and stability-indicating pre-column derivatization HPLC method for the determination of AMK in pure and parenteral dosage forms. Methods: The stock solution of AMK was derivatized prior to its analysis. The mobile phase used for the analysis was acetonitrile and water in the ratio of 50:50 (v/v) at pH 6.0. The method has been validated according to the guideline of International Council for Harmonization (ICH) and different parameters such as linearity, range, accuracy, precision, sensitivity, robustness, solution stability, specificity and system suitability have been studied. AMK was subjected to stress degradation studies including thermolysis, humidity exposure, acid-base hydrolysis, and oxidation in order to determine the specificity of the test method. Results: The retention time of AMK has been found to be 4.7 min. The results indicated that the method is linear in the concentration range of 12.5-125% and possesses high accuracy (99.88±0.42%), precision (( Conclusion: It was observed that the stress degradation studies do not affect the accuracy of the method. Hence the proposed method can be used for the assay of AMK and its parenteral dosage form.

The photodegradation of fromylmethylflavin (FMF), a major intermediate product in the photolysis of riboflavin, in the pH range 8.0–12.0 has been studied. FMF undergoes photodegradation by side–chain cleavage to give lumichrome (LC) and lumiflavin (LF) in alkaline solution. It is also degraded by the hydrolysis of isoalloxazine ring to form 1,2–dihydro–1–methyl–2–keto–3–quinoxaline carboxylic acid (KA) and 1,2,3,4–tetrahydro–1–methyl–2,3–dioxoquinoxaline (DQ) and is oxidized to carboxymethylflavin (CMF) in alkaline solution. The photodegradation of FMF follows simultaneous first–order kinetics to form the side–chain, ring cleavage and oxidation products. The apparent first–order rate constants (kobs) for these reactions have been determined and are in the range of 0.15 (pH 8.0) to 4.98 × 102 min–1 (pH 12.0). The rate constants for the formation of the photoproducts (LC, LF, CMF, KA, DQ) have also been determined. The formation of the photoproducts is enhanced with pH due to the sensitivity of flavin triplet to alkaline hydrolysis. FMF and photodegradation products have been determined by a multicomponent spectrofluorimetric method in degraded solutions. It involves the separation of LC and LF by chloroform extraction at pH 2 followed by the choloroform extraction of undegraded FMF at pH 6.5 and their assay at 478 (LC) and 530 nm (LF and FMF), respectively. The aqueous phase is used for the assay of CMF, KA and DQ at 530, 443 and 420 nm, respectively. The mode of photodegradation of FMF has been discussed.

This is the first study on the photolysis of carboxymethylflavin (CMF), an intermediate in the photolysis of riboflavin (RF). CMF is photodegraded by removal of side-chain to lumichrome (LC) in acid solution and to LC and lumiflavin (LF) in alkaline solution. It also undergoes alkaline hydrolysis to 1,2-dihydro-1-methyl-2-keto-3-quinoxaline carboxylic acid (KA) and 1,2,3,4-tetrahydro-1-methyl-2,3-dioxoquinoxaline (DQ) by cleavage of isoalloxazine ring. CMF degrades to LC in organic solvents. The formation of LC in acid solution and organic solvents takes place by second-order reaction and those of LC, LF, KA and DQ in alkaline solution by first-order reactions. The values of second-order rate constants for the photolysis of CMF at pH 2.0 to 7.0 are in the range of 1.13 to 2.45 M−1 s−1 and those of first-order rate constants (kobs) at pH 8.0–12.0 from 1.53 to 4.18 × 10−4 s−1 and for the formation of photoproducts from 0.37 to 16.6 × 10−5 s−1. The photolysis of CMF is enhanced, with pH, in the alkaline region since the excited state is sensitive to alkaline hydrolysis. The photolysis and fluorescence quantum yields of CMF in aqueous and organic solvents have been reported. CMF and photoproducts have been assayed spectrofluorimetrically. The mode of CMF photolysis is discussed.

Electric field driven reversible phase transitions in two-dimensional (2D) materials are appealing for their potential in switching applications. Here, we introduce potassium intercalated MnO2 as an exemplary case. We demonstrate the synthesis of large-area single-crystal layered MnO2 via chemical vapor deposition as thin as 5 nm. These crystals are spontaneously intercalated by potassium ions during the synthesis. We showed that the charge transport in 2D K-MnO2 is dominated by motion of hydrated potassium ions in the interlayer space. Under a few volts bias, separation of potassium and the structural water leads to formation of different phases at the opposite terminals, and at larger biases K-MnO2 crystals exhibit reversible layered-to-spinel phase transition. These phase transitions are accompanied by electrical and optical changes in the material. We used the electric field driven ionic motion in K-MnO2 based devices to demonstrate the memristive capabilities of two terminal devices.

Mechanical properties of transition metal dichalcogenides (TMDCs) are relevant to their prospective applications in flexible electronics. So far, the focus has been on the semiconducting TMDCs, mostly MoX2 and WX2 (X = S, Se) due to their potential in optoelectronics. A comprehensive understanding of the elastic properties of metallic TMDCs is needed to complement the semiconducting TMDCs in flexible optoelectronics. Thus, mechanical testing of metallic TMDCs is pertinent to the realization of the applications. Here, we report on the atomic force microscopy-based nano-indentation measurements on ultra-thin 2H-TaS2 crystals to elucidate the stretching and breaking of the metallic TMDCs. We explored the elastic properties of 2H-TaS2 at different thicknesses ranging from 3.5 nm to 12.6 nm and find that the Young's modulus is independent of the thickness at a value of 85.9 +/- 10.6 GPa, which is lower than the semiconducting TMDCs reported so far. We determined the breaking strength as 5.07 +/- 0.10 GPa which is 6% of the Young's modulus. This value is comparable to that of other TMDCs. We used ab initio calculations to provide an insight into the high elasticity measured in 2H-TaS2. We also performed measurements on a small number of 1T-TaTe2, 3R-NbS2 and 1T-NbTe2 samples and extended our ab initio calculations to these materials to gain a deeper understanding on the elastic and breaking properties of metallic TMDCs. This work illustrates that the studied metallic TMDCs are suitable candidates to be used as additives in composites as functional and structural elements and for flexible conductive electronic devices.

Cataloged from PDF version of article. Thesis (M.S.): Bilkent University, Department of Physics, İhsan Doğramacı Bilkent University, 2020. Includes bibliographical references (leaves 80-92). In 2004, successful isolation of graphene attracted immense attention of scientists because of atomic scale thickness and exotic functionalities. Regardless of graphene’s thickness and extraordinary properties only reason that limits the usage of graphene in electronics is no band gap. But there is a way to open band gap of graphene by introducing defects or applying electric field but defects introduction can affect its functionality. So, world moved towards transition metal dichalcogenides (TMDCs), new analogs of graphene with thickness dependent band gap option are promising nominee for potential applications in modern physics and electronics. Besides electronic properties, TMDCs depict excellent mechanical characteristics (in plane elastic modulus, breaking strength/strain and pretension) compared to conventional volumetric counterparts. The objective of this study is to investigate work function and mechanical properties of atomically thin materials using Kelvin probe force microscopy (KPFM) and Nanoindentation modes of Asylum Atomic Force Microscopy (AFM) respectively. Firstly, KPFM experiments were performed on CVD grown Vanadium Sesquioxide V2O3 to map surface potential variation and calculated work function value 4.91 eV. This will help in understanding band alignment, contact resistance and appropriate Schottky barrier height (SBH) by choosing metal contacts with closer work function to V2O3. Secondly by using AFM based nanoindentation we first time reported elastic features of metallic TMDCs: 2H-TaS2, 3R-NbS2, 1T-TaTe2 and 1T-NbTe2 with various thickness values suspended over circular holes. Comprehensive measurement was done on 2H-TaS2 and found thickness independent Young’s modulus for 2H-TaS2 is 114 ± 14 GPa, breaking strength 12.6 ± 2.6 GPa corresponds to nominal strain of 11% and ultimate strain of 0.22. Same mechanical features were investigated for other three materials and they also manifested extreme elasticity and high strain values compare to other 2D materials reported so far except graphene. This mechanical analysis of metallic materials will contribute in future flexible nano technological devices (for instance piezo electronics), wearable electronics, resistive coatings in electronic devices, nanoelectromechanical systems (NEMS) and strain sensors. by Ali Sheraz M.S.

Tolfenamic acid (TA) is commonly used in humans and animals because of its anti-inflammatory, antipyretic, and analgesic effects. So far, no study has been carried out to develop a validated spectrofluorimetric method for determination of TA. Therefore, the present study aimed to develop and validate a simple, accurate, rapid, economical, and precise spectrofluorimetric method to assay TA in its pure and dosage forms, and also in degraded solutions. The fluorimetric method had higher sensitivity compared with the spectrophotometric and high-performance liquid chromatography methods and could determine the drug at the microgram level. Optimum pH of TA for maximum fluorescence intensity was 3, and its two pKa values were calculated as 1.95 and 4.05. The proposed method was validated according to the guidelines of the International Council for Harmonisation, and parameters such as linearity, range, accuracy, precision, sensitivity, robustness, specificity, and solution stability were tested. Stress-induced degradation studies on TA did not affect the accuracy and precision of the proposed method. The results obtained indicated that the method was linear over the concentration range 0.2-0.9 × 10-3 M with good accuracy, precision, and robustness for assay of TA in its pure and its tablet dosage forms and was comparable statistically with the British Pharmacopoeia method.

A stability-indicating spectrofluorimetric method has been developed for the simultaneous assay of riboflavin (RF) and photoproducts, formylmethylflavin (FMF), lumichrome (LC) and lumiflavin (LF) in aqueous solution. The method is based on the extraction of LC formed in acid solution and LC and LF formed in alkaline solution with chloroform at pH 2.0 and their assay by fluorescence measurements at 478 and 530 nm, respectively. The aqueous phase, on readjustment of the pH to 6.5, is used to extract FMF with chloroform and its assay is carried out at 530 nm. The aqueous phase is then used for the assay of RF at 530 nm. The proposed method gives more accurate results for the assay of RF compared to those of the United States Pharmacopeia (USP) spectrofluorimetric method which does not take into account the presence of RF photoproducts having similar fluorescence characteristics. The proposed method along with the USP method has been applied to the study of the kinetics of photolysis of RF, assay of stored commercial vitamin preparations and their radiated samples. The results show that the USP method does not distinguish between the fluorescence of RF and its photoproducts, and, therefore, gives erroneous results with about 11% excess in the quantity of the vitamin compared to that of the proposed method. This is due to the interference of the fluorescence of photoproducts in the assay of RF. The method has been validated for various analytical parameters according to the guideline of the International Council for Harmonization (ICH).

The photodegradation of ascorbic acid (AH2) in the presence of nicotinamide (NA) at pH 2.0–12.0 has been studied using a 30 W UV radiation source. The reaction follows first-order kinetics and the values of apparent first-order rate constants (kobs) at 1 × 10−3 M NA concentration range from 1.17 (pH 2.0) to 3.61 × 10−3 min−1 (pH 12.0). The values of these rate constants (k0) in the absence of NA range from 0.50 (pH 2.0) to 1.75 × 10−3 min−1 (pH 12.0), indicating that the values of kobs for the photodegradation of AH2 in the presence of NA are about 2 fold compared to those of the AH2 alone. The second-order rate constants (k') for the photochemical interaction of AH2 and NA are in the range of 0.67 (pH 2.0) and 1.86 × 10−3 M−1 min−1 (pH 12.0). The k'-pH profile shows a gradual increase in the rate as a function of pH. This is due to the ionization of AH2 to give ascorbyl anions (AH−) which are more susceptible to photodegradation compared to the neutral molecule (AH2). NA appears to undergo photochemical interaction with AH2 during the reaction by acting as an electron acceptor to enhance its rate of photodegradation. The concentrations of AH2 and NA in degraded solutions have been determined by a two-component spectrometric method at 243 and 261 nm (pH 2.0) with a precision of ±2%. The method has been validated and the results are comparable to the HPLC method.

The effect of metal ion complexation on the photolysis of riboflavin (RF) using various metal ions (Ag+, Ni2+, Co2+, Fe2+, Ca2+, Cd2+, Cu2+, Mn2+, Pb2+, Mg2+, Zn2+, Fe3+) has been studied. Ultraviolet and visible spectral and fluorimetric evidence has been obtained to confirm the formation of metal-RF complexes. The kinetics of photolysis of RF in metal-RF complexes at pH7.0 has been evaluated. The apparent first-order rate constant (kobs) for the photolysis of RF and the formation of lumichrome (LC) and lumiflavin (LF) (0.001M phosphate buffer) and LC, LF and cyclodehydroriboflavin (CDRF) (0.2-0.4M phosphate buffer) have been determined. The values of kobs indicate that the rate of photolysis of RF is promoted by divalent and trivalent metal ions. The second-order rate constants (k' ) for the interaction of metal ions with RF are in the order: Zn2+>Mg2+>Pb2+>Mn2+>Cu2+>Cd2+>Fe2+>Ca2+>Fe3+>Co2+>Ni2+>Ag+. In phosphate buffer (0.2-0.4M), an increase in the metal ion concentration leads to a decrease in the formation of LC compared to that of CDRF by different pathways. The photoproducts of RF have been identified and RF and the photoproducts have simultaneously been assayed by a multicomponent spectrometric method. The mode of photolysis of RF in metal-RF complexes has been discussed.

The photolysis of cyanocobalamin (B 12 ) and aquocobalamin (B 12a )/hydroxocobalamin (B 12b ) in the presence of ascorbic acid (AH 2 ) at pH 2.0–12.0, under aerobic conditions, has been studied. It follows first–order kinetics and the values of apparent first–order rate constants ( k obs ) at pH 2.0–12.0 range from 0.37 to 2.63 × 10 −4 s −1 and 0.21–6.35 × 10 −4 s −1 , for B 12 and B 12a /B 12b , respectively. The second–order rate constants ( k 2 ) for the photochemical interaction of AH 2 and B 12 and AH 2 and B 12a /B 12b range from 0.20 (pH 2.0) to 1.09 × 10 −2 M −1 s −1 (pH 5.0) and 5.88 (pH 2.0) to 91.08 × 10 −2 M −1 s −1 (pH 5.0), respectively. The values of the k 2 for AH 2 –B 12a /B 12b interaction are 30–80 times greater than those of AH 2 –B 12 suggesting a greater susceptibility of B 12a /B 12b to photodegradation compared to that of B 12 in this pH range. The k 2 –pH profiles for both B 12 and B 12a /B 12b are bell–shaped curves indicating the effect of AH 2 ionization on the rates of interaction. The complete discoloration of B 12 and B 12a /B 12b solutions on prolonged photolysis indicates the formation of corrin ring cleavage (oxidation) products in acid and alkaline solutions. These oxidation products do not absorb in the visible region. Reaction schemes for the mode of photodegradation of B 12 and B 12a /B 12b in the presence of AH 2 have been presented.

Pharmaceutical preparations may contain a single ingredient or multi-ingredients as well as excipients. In multicomponent systems, specific analytical methods are required to determine the concentrations of individual components in the presence of interfering substances. Ultraviolet and visible spectrometric methods have widely been developed for the analysis of drugs in mixtures and pharmaceutical preparations. These methods are based on ultraviolet and visible multicomponent analysis and chemometrics (multivariate data analysis). The commonly used chemometric methods include principal component analysis (PCA); regression involving classical least squares (CLS), partial least squares (PLS), inverse least squares (ILS), principal component regression (PCR), multiple linear regression (MLR), artificial neural networks (ANNs); soft independent modeling of class anthology (SIMCA), PLS-discriminant analysis (DA); and functional data analysis (FDA). In this chapter, the applications of multicomponent ultraviolet and visible, derivative, infrared and mass spectrometric and spectrofluorimetric methods to the analysis of multi-ingredient pharmaceutical preparations, biological samples and the kinetics of drug degradation have been reviewed. Chemometric methods provide an efficient solution to calibration problems in the analysis of spectral data for the simultaneous determination of drugs in multicomponent systems. These methods facilitate the assessment of product quality and enhance the efficiency of quality control systems.

Pharmaceutical preparations may contain a single ingredient or multi-ingredients as well as excipients. In multicomponent systems, specific analytical methods are required to determine the concentrations of individual components in the presence of interfering substances. Ultraviolet and visible spectrometric methods have widely been developed for the analysis of drugs in mixtures and pharmaceutical preparations. These methods are based on ultraviolet and visible multicomponent analysis and chemometrics (multivariate data analysis). The commonly used chemometric methods include principal component analysis (PCA); regression involving classical least squares (CLS), partial least squares (PLS), inverse least squares (ILS), principal component regression (PCR), multiple linear regression (MLR), artificial neural networks (ANNs); soft independent modeling of class anthology (SIMCA), PLS-discriminant analysis (DA); and functional data analysis (FDA). In this chapter, the applications of multicomponent ultraviolet and visible, derivative, infrared and mass spectrometric and spectrofluorimetric methods to the analysis of multi-ingredient pharmaceutical preparations, biological samples and the kinetics of drug degradation have been reviewed. Chemometric methods provide an efficient solution to calibration problems in the analysis of spectral data for the simultaneous determination of drugs in multicomponent systems. These methods facilitate the assessment of product quality and enhance the efficiency of quality control systems.

Sensors are prone to environmental disturbances which introduces error in the sensor data and therefore the data becomes very unreliable and it cannot be used in precise electronic measurement systems. In this paper a software filter is applied that reduces this noise. The Kalman filter is an iterative filter that can reduce the error in the sensor data in real-time. These filters are regularly used in odometry and tracking applications, however, Kalman filters are very task specific. A generalized filter is proposed here that can be applied to multiple sensor types. Noisy data from temperature sensor, LDR and a flex sensor was acquired and the Kalman filtere was applied to it. when the raw sensor data was plotted side by side with the filtered data, the latter produced a smoother output waveform. The effect of different Kalman gain values was also tested on the sensors and it resulted in a delayed estimated signal.

The present study has been carried out to validate a UV spectrometric method for the assay of tolfenamic acid (TA) in organic solvents. TA is insoluble in water; therefore, a total of thirteen commonly used organic solvents have been selected in which the drug is soluble. Fresh stock solutions of TA in each solvent in a concentration of 1 × 10−4 M (2.62 mg%) were prepared for the assay. The method has been validated according to the guideline of International Conference on Harmonization and parameters like linearity, range, accuracy, precision, sensitivity, and robustness have been studied. Although the method was found to be efficient for the determination of TA in all solvents on the basis of statistical data 1-octanol, followed by ethanol and methanol, was found to be comparatively better than the other studied solvents. No change in the stock solution stability of TA has been observed in each solvent for 24 hours stored either at room (25±1°C) or at refrigerated temperature (2–8°C). A shift in the absorption maxima has been observed for TA in various solvents indicating drug-solvent interactions. The studied method is simple, rapid, economical, accurate, and precise for the assay of TA in different organic solvents.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently a global pandemic with unprecedented public health, economic and social impact. The development of effective mitigation strategies, therapeutics and vaccines relies on detailed genomic and biological characterization of the regional viruses. This study was carried out to isolate SARS-CoV-2 viruses circulating in Anatolia, and to investigate virus propagation in frequently-used cells and experimental animals. We obtained two SARS-CoV-2 viruses from nasopharngeal swabs of confirmed cases in Vero E6 cells, visualized the virions using atomic force and scanning electron microscopy and determined size distribution of the particles. Viral cytopathic effects on Vero E6 cells were initially observed at 72 h post-inoculation and reached 90% of the cells on the 5th day. The isolates displayed with similar infectivity titers, time course and infectious progeny yields. Genome sequencing revealed the viruses to be well-conserved, with less than 1% diversity compared to the prototype virus. The analysis of the viral genomes, along with the available 62 complete genomes from Anatolia, showed limited diversity (up to 0.2% on deduced amino acids) and no evidence of recombination. The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%. The isolates produced non-fatal infection in the transgenic type I interferon knockout (IFNAR−/-) mice, with varying neutralizing antibody titers. Hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy, with similar histopathological and immunohistochemistry findings in the lungs, heart, stomach, intestines, liver, spleen and kidneys. Peak viral loads were detected in the lungs, with virus RNA present in the kidneys, jejunum, liver, spleen and heart. In conclusion, we characterized two local isolates, investigated in vitro growth dynamics in Vero E6 cells and identified IFNAR−/− mice as a potential animal model for SARS-CoV-2 experiments., Bioinformatics; Microbiology; Virology; Viral disease; Viral genetics; Epidemiology; Respiratory system; SARS-CoV-2; Isolate; Genome; IFNAR−/- mice

This investigation involves a study of the photochemical interaction of riboflavin (RF) and bovine serum albumin (BSA) in aqueous solution and the evaluation of this effect on the photostabilization of RF. RF solution (5 × 10–5 M) were irradiated with visible light in the presence of BSA (4.0–6.0 × 10–5 M) at pH 7.4 (0.005 M, phosphate buffer saline) and the apparent first–order rate constants for the photolysis of RF were found to be in the range of 3.92–9.26 × 10–3 min–1. The rate of RF photolysis is inhibited with an increase in the concentration of BSA. The second–order rate constant for the photochemical interaction of RF and BSA at pH 7.4 is 1.22 M–1 min–1. There is a gradual loss of RF fluorescence with an increase in BSA concentration due to the formation of a non–fluorescent complex between the two molecules. The value of Stern-Volmer quenching constant has been determined as 2.673 × 103 M–1. A two-component spectrometric method with correction for irrelevant absorption caused by BSA components has been used to determine RF and its photoproduct, lumichrome (LC), in photolyzed solutions. The mode of photochemical interaction of RF and BSA has been discussed.

The photolysis of thiochrome (THC), an oxidation product of thiamine (vitamin B1) (THE), used for its fluorimetric assay, has been studied in the pH range 7.0–12.0. THC undergoes photooxidation to oxodihydrothiochrome (ODTHC) which is oxidized to a non-fluorescent compound (OP1) on UV irradiation. The kinetics of the consecutive first-order reactions: THC → k 1 ODTHC → k 2 OP 1 , has been evaluated and the values of first-order rate constants, k1 (0.58–4.20 × 10−5, s−1) and k2 (0.05–2.03 × 10−5, s−1), at pH 7.0–12.0 have been determined. The rates of degradation of THC and ODTHC are enhanced with pH and the second-order rate constants k1ʹ and k2ʹ for the OH– ion-catalyzed reaction are in the range of 0.002–58.3 M−1 s−1. The quantum yields of the photolysis of THC and ODTHC in the pH range 7.0–12.0 have been determined. THC, ODTHC and OP1 have been identified by chromatographic, spectrometric and fluorimetric methods. THC and ODTHC have similar fluorescence characteristics and emit at 450 and 445 nm, respectively. THC, ODTHC and OP1 with distinct absorption maxima (370, 344 and 290 nm, respectively) have been determined by a newly developed and validated multicomponent spectrometric method during the photolysis reactions. The on-line formation of THC by the photooxidation of THE may lead to the degradation of THC and give erroneous results in the fluorimetric assay of THE. A scheme for the photolysis reactions of THC in aqueous solution is presented.

The simultaneous assay of carboxymethylflavin (CMF), an intermediate in the photolysis of riboflavin, and its hydrolytic side-chain cleavage products, lumichrome (LC) (acid solution) and LC and lumiflavin (LF) as well as isoalloxazine ring cleavage products, 1,2-dihydro-1-methyl-2-keto-3-quinoxaline carboxylic acid (KA) and 1,2,3,4-tetrahydro-1-methyl-2,3-dioxo-quinoxaline (DQ) (alkaline solution) has been carried out by a multicomponent spectrofluorimetric method. The method is based on the adjustment of pH of the degraded solutions to 2.0 and extraction of LC and LF with chloroform. The chloroform extract is evaporated to dryness under reduced pressure, the residue dissolved in pH 6.5 citro-phosphate buffer and LC and LF determined at their fluorescence maxima at 478 and 530 nm, respectively. The pH of the aqueous phase is re-adjusted to 6.5 and the solution used for the determination of CMF, KA and DQ at the wavelengths of 530, 443 and 420 nm, respectively. The proposed method has been validated according to ICH guidelines. The calibration curves for CMF and its hydrolytic products are linear in the concentration range of 0.5-5.0 × 10-6 M. The mean recovery ranges from 99.0-102.0% with relative standard deviation (RSD) of 0.19-0.99%. The limit of detection (LOD) and the limit of quantification (LOQ) are in the range of 1.17-1.78 × 10-7 M and 3.55-5.40 × 10-7 M, respectively. The uniformity of molar balance of CMF and degradation products during hydrolytic reactions indicates the accuracy of the proposed method for the spectrofluorimetric assay of the compounds. It has been applied to study the kinetics of hydrolytic reactions of CMF.

Tolfenamic acid (TA) is a nonsteroidal antiinflammatory drug and belongs to the group of fenamates. It is used as a potent pain reliever in the treatment of acute migraine attacks, and disorders like dysmenorrhea, rheumatoid, and osteoarthritis. TA has shown excellent in vitro antibacterial activity against certain ATCC strains of bacteria when complexed with bismuth(III). It has also been reported to block pathological processes associated with Alzheimer's disease. In the recent past, TA has also been used as a novel anticancer agent for the treatment of various cancers. In view of the clinical importance of TA, a comprehensive review of the physical and pharmaceutical properties and details of the various analytical methods used for the assay of the drug in pharmaceutical and biological systems has been made. The methods reviewed include identification tests and titrimetric, spectrophotometric, chromatographic, electrochemical, thermal, microscopic, enzymatic, and solid-state techniques. Along with the analytical profile, the stability and degradation of TA, its pharmacology and pharmacokinetics, dosage forms and dose, adverse effects and toxicity, and interactions have been discussed.