Cost-effective, green HPLC determination of losartan, valsartan and their nitrosodiethylamine impurity: application to pharmaceutical dosage forms.

Angiotensin-converting enzyme inhibitors are one of the most widely used anti-hypertensive drugs which are used to reduce hypertension. In 2018, the United States Food and Drug Administration together with the European Medicine Agency declared the presence of carcinogenic nitrosamine impurities such as nitrosodiethylamine (NDEA) in some of the products, including valsartan (VLS) and losartan (LOS), and drugs' recall procedures were started. Thus, they should be controlled to be below the acceptable cancer risk level to ensure safety of the pharmaceutical products. Therefore, sensitive and reliable analytical methods were required for detection and quantitation of NDEA in bulk and finished drug products. Green analytical chemistry has received great interest to minimize the amount of organic solvents consumed without loss in chromatographic performance. A green and sensitive HPLC method was developed for the determination of NDEA in LOS and VLS using mobile phase of 0.02 M ammonium acetate adjusted to pH 7.2 and ethanol in gradient manner. Limits of detection and limits of quantification for NDEA were estimated to be 0.2 and 0.5 µg ml-1, respectively. The standardized limits of NDEA impurity in drug substances were set as 0.56 ppm, which indicates the feasibility of its determination by the proposed conventional method without need for expensive instrumentations (e.g. MS/MS detectors) that are not found in most pharmaceutical quality control laboratories.

Silver Nanoparticles Synthesis for Sensitive Spectrophotometric Determination of Sofosbuvir, Lamivudine, and Ritonavir in Pure Forms and Pharmaceutical Dosage Forms.

BACKGROUND: Silver nanoparticles synthesis is now widely applicable as a method for sensitive spectrophotometric determination of many pharmaceuticals. OBJECTIVE: A highly sensitive, cheap, green, nonextractive, and accurate spectrophotometric method was developed for the determination of three important antiviral drugs. METHODS: The method depends on the formation of silver nanoparticles as a result of the redox reaction between antiviral drugs as a reducing agent and AgNO3 as an oxidizing agent in presence of polyvinyl pyrrolidone as a stabilizing agent. The UV absorbance of the resulted golden yellow silver nanoparticles can be easily measured at 421 nm for Sofosbuvir (SFS) and Ritonavir (RIT) and at 425 nm for Lamivudine (LAM). RESULTS: The LODs were 23.5, 30, and 21.5 nm/mL for SFS, LAM, and RIT, respectively. The LOQs were 70.5, 90, and 64.6 nm/mL for SFS, LAM, and RIT, respectively. The method was validated according to International Conference on Harmonization guidelines, and it was successively applied for the determination of the studied drugs in their different pharmaceutical dosage forms and gave excellent percent of recovery. The results showed excellent agreement with the reported method with respect to precision and accuracy. CONCLUSIONS: Being simple, fast, robust, and economic, this method is eligible for use in the routine work in pharmaceutical quality control laboratories. HIGHLIGHTS: A sensitive and economic spectrophotometric method was developed and validated for quantitative determination of SFS, LAM, and RIT. The method was validated and applied for determination of the studied drugs in their different formulations. The method used water as the main solvent, so our proposed method is considered environmentally friendly.

Core-shell particles and monolithic columns; tools for simultaneous LC analysis of avanafil, sildenafil, apomorphine, trazodone, yohimbine, tramadol and dapoxetine in pharmaceutical dosage forms, counterfeit products and human plasma.

By 2025, it's estimated that 322 million males worldwide will suffer from sexual disorders. This can give an estimation for the size of the pharmaceutical and counterfeit products industry for the next few years. Meanwhile, green analytical chemistry forced itself to decrease the massive environmental pollution and hence new analytical methodologies are needed to replace the old ones that consume large amounts of hazardous solvents. In this research, two new methods were validated for determination of seven recognized drugs used in treatment of male impotence, premature ejaculation as well as enhancing sexual libido by HPLC on RP-C18 core-shell particulate and monolithic columns. The study was extended to compare the capabilities of those stationary phases to accommodate greener chromatography concepts without loss of efficiency. Both morphologies shortened the analysis time relative to the previously reported conventional HPLC methods by different approaches. Core-shell particles had higher efficiency in terms of theoretical plates' number and enhanced resolution power which enabled lower detection limits. However, the monolithic column had lower column backpressure which enabled the use of ethanol as a greener alternative solvent at even higher flow rates. The methods were finally applied successfully for the determination of drugs under study in pharmaceutical dosage forms, counterfeit products and in human plasma.

Development and validation of eco-friendly micellar-HPLC and HPTLC-densitometry methods for the simultaneous determination of paritaprevir, ritonavir and ombitasvir in pharmaceutical dosage forms.

Ombitasvir, ritonavir and paritaprevir are three recently discovered directly acting antiviral drugs (DAADs) used in combined single dose tablet dosage form for treatment of hepatitis-C viral infections (HCV). The methods of analysis followed by quality control and research laboratories are required to be economic and fast; however, these methods can also produce huge amounts of chemical waste. In this study two fast, economic and green HPLC and HPTLC methods were validated for the simultaneous determination of the three drugs. For HPLC, isocratic elution used a mixture of micellar aqueous mobile phase consisting of (0.15 M sodium lauryl sulfate and 0.01 M sodium dihydrogen phosphate, pH 6.2) and ethanol (56:44). Elution was done on RP-C18 Kinetix® column (5 µm, 150 mm × 4.6 mm ID) at flow 1 mL min-1 and 254 nm UV-detector. HPTLC separations were performed on Merck® (20 cm × 10 cm) aluminum HPTLC plates coated with silica gel 60F254 using a mobile phase, Methylene chloride: methanol: ethyl acetate: ammonia (25%), (5:1:3:1, v/v/v/v) respectively. The calibration curves were linear across ranges of 3-100 µg mL-1 and 0.1-2 µg/spot for both HPLC and HPTLC methods, respectively. The two methods were applied successfully for the determination of the three drugs under study in their combined tablets dosage forms.

Development of a highly sensitive high-performance thin-layer chromatography method for the screening and simultaneous determination of sofosbuvir, daclatasvir, and ledipasvir in their pure forms and their different pharmaceutical formulations.

The combination of sofosbuvir and daclatasvir or sofosbuvir and ledipasvir is now widely used as an ideal treatment for hepatitis C virus infection. For this purpose, a simple, sensitive, accurate, economic, and precise high-performance thin-layer chromatography was developed and validated for the determination of sofosbuvir, daclatasvir, and ledipasvir in their pure form as well as their different pharmaceutical products. The method used Merck high-performance thin-layer chromatography aluminum plates precoated with silica gel 60 F254 as a stationary phase and mobile phase consisting of methylene chloride/methanol/ethyl acetate/ammonia (25%) (6:1:4:1, v/v/v/v). This system was found to give compact symmetric peaks of sofosbuvir, daclatasvir, and ledipasvir with retardation factors of 0.27 ± 0.01, 0.50 ± 0.007, and 0.68 ± 0.008, respectively. The densitometric scanner was set at 275 nm using a deuterium lamp. The calibration curves were linear over the range of 100-3000 ng/spot for sofosbuvir, and daclatasvir, and range of 50-3000 ng/spot for ledipasvir. The detection limits were 22.5, 31.90, and 15.80 for sofosbuvir, daclatasvir, and ledipasvir. The quantitation limits were 67.50, 95.60, and 47.50 for sofosbuvir, daclatasvir, and ledipasvir. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines and the results were acceptable.

Performance Comparison Between Monolithic, Core-Shell, and Totally Porous Particulate Columns for Application in Greener and Faster Chromatography.

Background: The introduction of monolithic rods and core-shell particles as new morphologies of packing materials different from the conventional totally porous particles resulted in a leap forward for performance in LC. Meanwhile, environmental safety has become increasingly important in many areas, especially in industry and research laboratories. Objective: This study compared the efficiencies of commercially available columns of different lengths and diameters when greener chromatographic conditions were utilized. The main purpose of this study is to help practitioners select the most appropriate stationary phase for faster and greener analysis. Methods: The three types of stationary phases were compared in terms of separation efficiency, number of theoretical plates, peak shape, selectivity, resolution, analysis time, mobile phase consideration, and permeability using six drug molecules. Results: Results indicated that core-shell and monolithic stationary phases had superiority over the conventional totally porous particles in terms of efficiency and speed of analysis. Monolithic rods had lower column backpressure and higher permeability, so they are more suitable for higher mobile phase flow rates and viscosities. However, core-shell particles provided enhanced peak shapes and number of theoretical plates. Conclusions: The choice will depend on the main purpose of analysis and the composition of the mobile phase. Compromise must be made to obtain the best trade-off between separation efficiency and analysis speed. Highlights: This study is the first to consider green chromatography concepts for the selection of the best stationary phase of new morphologies.

Comparison between core-shell and totally porous particle stationary phases for fast and green LC determination of five hepatitis-C antiviral drugs.

The performances of core-shell 2.7 µm and fully porous sub-2 µm particles packed in narrow diameter columns were compared under the same chromatographic conditions. The stationary phases were compared for fast separation and determination of five new antiviral drugs; daclatasvir, sofosbuvir, velpatasvir, simeprevir, and ledipasvir. The gradient elution was done using ethanol as green organic modifier, which is more environmentally friendly. Although both columns provided very good resolution of the five drugs, core-shell particles had proven to be of better efficiency. Under gradient elution conditions, core-shell particles exhibited faster elution, better peak shape, and enhanced resolution adding to lower system backpressure. The column backpressure on sub-2 µm particles was more than twice that on core-shell particles. This gives a chance to use conventional high-performance liquid chromatography conditions without needing special instrumentation as that required for ultra-high performance liquid chromatography. The method was validated for determination of the five drugs by gradient elution using mobile phase composed of organic modifier ethanol and aqueous part containing 0.75 g sodium octane sufonate and 3.0 g sodium dihydrogen phosphate per liter at pH of 6.15. Detection was done using UV-detector set at 210 nm. The linearity, accuracy, and precision were found very good within the concentration range of 2-200 µg/mL.

Chromatographic analysis of some drugs employed in erectile dysfunction therapy: qualitative and quantitative studies using calixarene stationary phase.

In this study, the effect of change in chromatographic process variables on the retention behavior of four drugs employed in erectile dysfunction therapy on a calixarene stationary phase is described. Three of these drugs are known to treat erectile dysfunction, namely, sildenafil citrate, tadalafil, and apomorphine hydrochloride, and one drug that is used as opioid analgesic, tramadol hydrochloride, which is quiet widely misused to treat premature ejaculation. The results indicate the importance of considering the structure and pKa values of drugs to be separated along with mobile phase composition. A new optimized, rapid, and accurate liquid chromatography method is also established for simultaneous determination of sildenafil citrate, tadalafil, and apomorphine hydrochloride in pharmaceutical preparations and bulk powders. The chromatographic separation of the three pharmaceuticals was achieved on a calixarene column in less than 10 min using a binary mobile phase of 35% acetonitrile and 65% 50 mM sodium perchlorate pH2.5 at 1 mL/min flow rate. The method was validated for system efficiency, linearity, accuracy, precision, limits of detection and quantitation, specificity, stability, and robustness. Statistical analysis proved that the method enabled reproducible and selective quantification of all three analytes in bulk drugs and in pharmaceutical preparations.