Validated chromatographic methods for determination of teriflunomide and investigation of its intrinsic stability.

Two rapid, precise, and sensitive stability-indicating high performance chromatographic methods for the measurement of Teriflunomide in its degradation products' existence were developed. These were RP-HPLC and HPTLC using UV detector. HPLC separation was accomplished utilizing Thermo BDS hypercil C18 column (250 × 4.6 mm, 5 µm) and acetonitrile: 0.03 M potassium dihydrogen phosphate: triethylamine (50:50:0.1%, by volume) as mobile phase at flow rate of 1mL/min. The separated peaks were detected at 250.0 nm. The densitometric approach was conducted utilizing HPTLC 60 F254 silica gel plates, and a developing system of benzene: ethanol: acetic acid (7.5:1:0.25, by volume) and detection was done at 250.0 nm. The developed approaches were evaluated regarding the International Conference on Harmonization (ICH) instructions. The calibration curves of both techniques were constructed with linearity ranges of (5-100) µg/mL and (2-10) µg /band, for HPLC and densitometric determination, consecutively. Teriflunomide was exposed to base and acid hydrolysis, oxidation using H2O2 and finally, thermal degradation as stated in ICH guidelines. The degradation product structures' elucidation was achieved through LC-MS.

Electrochemically-selective electrode for quantification of dorzolamide in bulk drug substance and dosage form.

Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding ß-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods.

A chemically modified solid-state sensor for magnesium(ii) ions and esomeprazole magnesium potentiometric assay.

The use of electrochemical sensors offers a simple, affordable solution with great reliability. Magnesium is a mineral that the body requires to function properly. It encourages preserving a stable pulse, strong bones, and healthy blood pressure. Herein, a novel ion-selective electrode using esomeprazole magnesium trihydrate as an ion-association complex was developed for magnesium(ii) ion determination in mineral water, drug substances, and pharmaceutical formulations. The electrode response was optimized in terms of plasticizer type, ion exchanger concentration, and membrane composition. To find the best sensor combination, the initial optimization research was performed using eight different sensors. A membrane containing 20% esomeprazole magnesium trihydrate, 36% carbon, and 44% o-Nitrophenyl Octyl Ether (NPOE) as a plasticizer yielded the best potentiometric response. The developed sensor demonstrated a Nernstian response with a slope of 29.93 ± 0.1 mV per decade in the concentration range of 1.41 × 10-5 mol L-1 to 1 × 10-2 mol L-1. Within a pH range of 5-8, it had a low detection limit of 4.13 × 10-6 mol L-1. When compared to the official method, there are no statistically significant differences.

Development and Validation of HPLC Fluorescence and UPLC/DAD Stability-Indicating Methods for Determination of Hepatitis C Antiviral Agent Daclatasvir.

Background: Few stability-indicating chromatographic methods were published for determination of daclatasvir. All used UV detection. Objective: This work aimed to develop rapid, specific, and novel stability-indicating methods using HPLC with fluorescence detection and ultra performance liquid chromatography (UPLC) with UV detection for the determination of daclatasvir in bulk powder and in its dosage form. Methods: The drug was subjected to hydrolysis (acidic and alkaline) as per International Conference on Harmonization (ICH) guidelines. The fragmentation pattern of the drug was studied using LC-MS. Separation was carried out first by HPLC using Thermo BDS Hypersil Phenyl (300 mm × 4 mm, 5 µm) column and a mobile phase consisting of ammonium phosphate buffer (0.02 M) pH 3-methanol (40+60, v/v) at flow rate 1 mL/min. Quantitation was achieved by fluorescence detection at 305 and 457 nm for excitation and emission, respectively. The second method used UPLC equipped with diode-array detector. Acquity BEH C18 (50 mm × 2.1 mm, 1.7 µm) column was used with the same mobile phase at flow rate 0.4 mL/min and detection wavelength at 305 nm. ICH guidelines were used for validation. Results: The mean percentage recovery ± SD values for tablet assay were found to be 101.12 ± 0.655 and 99.78 ± 0.632 by HPLC and UPLC methods, respectively. The assay results showed a good agreement with the reported method. Conclusions: The developed HPLC and UPLC methods provide simple, accurate, and reproducible analysis of daclatasvir without interference from degradates. Highlights: This is the first research using fluorescence detection in a stability-indicating chromatographic method for determination of daclatasvir.

Study of Oxyclozanide's Innate Stability Coupled with the Assessment of its Aquatic Photo-Transformation Using a Validated Isocratic HPLC Method.

Background: Oxyclozanide (OXY) is a veterinary medicine used for control of fascioliasis in farm animals. Literature review shows absence of sufficient information regarding its stability. Such information is important as it affects many stages of a drug's life cycle, from pharmaceutical manufacturing to its environmental fate understanding of the degradation of the drug once it is placed in the environment. Objective: An HPLC method was developed to address the impact of different stress conditions on OXY's stability. Methods: OXY's stability was investigated by exposure to forced acid and alkaline hydrolysis, thermal, oxidative and photolytic degradation, which are different stress conditions applied to the forced degradation study. Separation was performed on Eurosphere C18 analytical column (125 × 4.6 mm, 5 µm particle size) using 50 mM sodium acetate trihydrate (pH 4.5) and acetonitrile (50:50, v/v) as mobile phase and UV detection at 254 nm. A photolytic kinetics study was conducted by monitoring OXY photolysis under monochromatic and polychromatic light sources (UV lamp at 366 nm and natural sunlight) in aqueous buffers of different pHs (5, 7, and 9). LC-MS was used to identify the major photolytic degradate. Results: OXY was quantified over a concentration range of 1-80 µg/mL with mean recovery of 99.32 ± 1.80%. The drug was susceptible to oxidative and photolytic degradation. The photolytic kinetics were pH dependent. The LC-MS result supported photo-dehalogenation degradation mechanism. Conclusions: The developed method could be used in OXY stability testing. The results of the photolytic kinetics study can address OXY aquatic photo-transformation, thereby predicting its environmental fate and risks imposed on the ecosystem. Highlights: An HPLC method was developed for monitoring OXY degradation behavior and studying its photolytic kinetics with identification of its photodegradate.

Validated Stability-Indicating RP-HPLC Method for Simultaneous Determination of Clorsulon and Ivermectin Employing Plackett-Burman Experimental Design for Robustness Testing.

A sensitive and highly selective stability-indicating gradient HPLC method was developed and validated for simultaneous determination of clorsulon (CLO) and ivermectin (IVM) in the presence of their degradation products. The drugs were subjected to different stress conditions, including acid and alkaline hydrolysis, oxidative, thermal, and photolytic forced degradation. The robustness of the proposed method was assessed using the Plackett-Burman experimental design, the factors affecting system performance were defined, and nonsignificant intervals for the significant factors were determined. The separation was carried out on a ZORBAX SB phenyl analytical column (250 × 4.6 mm id, 5 µm particle size), with gradient elution utilizing 10 mM sodium dihydrogen phosphate and acetonitrile as mobile phase. UV detection was performed for CLO and IVM at 254 nm over a concentration range of 4-140 and 5-50 µg/mL, respectively, with mean percentage recoveries of 99.90 ± 1.30 and 98.59 ± 1.16%, respectively. The proposed method was successfully applied to a pharmaceutical dosage form containing the investigated drugs. The results were statistically compared with the official HPLC methods, and no significant differences were found.

Validated derivative and ratio derivative spectrophotometric methods for the simultaneous determination of levocetirizine dihydrochloride and ambroxol hydrochloride in pharmaceutical dosage form.

Three simple, precise, accurate and validated derivative spectrophotometric methods have been developed for the simultaneous determination of levocetirizine dihydrochloride (LCD) and ambroxol hydrochloride (ABH) in bulk powder and in pharmaceutical formulations. The first method is a first derivative spectrophotometric method ((1)D) using a zero-crossing technique of measurement at 210.4 nm for LCD and at 220.0 nm for ABH. The second method employs a second derivative spectrophotometry ((2)D) where the measurements were carried out at 242.0 and 224.4 nm for LCD and ABH, respectively. In the third method, the first derivative of the ratio spectra was calculated and the first derivative of the ratio amplitudes at 222.8 and 247.2 nm was selected for the determination of LCD and ABH, respectively. Calibration graphs were established in the ranges of 1.0-20.0 µg mL(-1) for LCD and 4.0-20.0 µg mL(-1) for ABH using derivative and ratio first derivative spectrophotometric methods with good correlation coefficients. The developed methods have been successfully applied to the simultaneous determination of both drugs in commercial tablet dosage form.