A Simple and Sensitive LC-MS/MS Method for Determination and Quantification of Potential Genotoxic Impurities in the Vismodegib Active Pharmaceutical Ingredient

A rapid and sensitive LC-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of four potential genotoxic impurities Imp-A (2-chloro-5-nitroaniline), Imp-B (1-chloro-2-iodo-4-nitrobenzene), Imp-C (1-(2-chloro-5-nitrophenyl)ethan-1-one) and Imp-D (2-chloro-5-nitrobenzoic acid) in Vismodegib API drug sample. This trace analysis was achieved on CSH C18, 15.0 cm x 3.0 mm, 1.7 micron column maintained at 45°C. Optimal mobile phase consisted of 0.05% formic acid in water was used as mobile phase A and acetonitrile used as mobile phase B in gradient mode with the flow rate of 0.5 mL/min. The developed method had the short run time of 12 minutes. Quantification of four potential genotoxic impurities were carried out using mass detection with electrospray ionization in multiple reaction monitoring mode. The method was linear in the range of 0.03 ppm to 1.50 ppm for four potential genotoxic impurities with a correlation coefficient not less than 0.999. The recoveries were found satisfactory over the range between 96.67 and 106.90% for all selected impurities. The developed method was able to quantitate all four PGIs at a concentration level of 0.03 ppm (0.03 ppm with respect to 20 mg /mL Vismodegib).

Development and Validation of Novel RP-HPLC Method for the Simultaneous Determination of Remogliflozin and Vildagliptin in Bulk and in synthetic Mixture

Vildagliptin which is DPP-4 inhibitor and Remogliflozin which is SGLT2 inhibitor in single dose regimen lower blood glucose by separate, complementary mechanisms. Both are glucose dependent, accounting for the low risk of hypoglycaemia during treatment. There is no risk factors associated with this combination and moreover it is single dose regimen. The aim of the present study was to develop and validate a simple, rapid and reproducible gradient high performance reverse phase liquid chromatography method for the estimation of Remogliflozin and Vildagliptin in bulk drug sample and in synthetic mixture using Xterra® Waters C18 column (150 mm×4.6 mm, 5 µm) at 25°C with UV detection at 210 nm and for this gradient mode was used. The compounds were eluted gradiently at a flow rate of 1.0ml/min. The average retention times for Remogliflozin and Vildagliptin were 4.881 and 6.334 min, respectively. The calibration curves were linear (r2 =0.988) over the concentration range 10-200 µg/ml for Remogliflozin and 10-200 µg/ml for Vildagliptin. No spectral or chromatographic interferences from formulation excipients were found and hence it was successfully applied for the determination of Remogliflozin and Vildagliptin in bulk and in synthetic mixture. The accuracy of the proposed method was determined by recovery studies and found to be 98-101%. The proposed method was validated and results conformed to ICH parameters.

UV SPECTROSCOPY DETERMINATION OF CILAZAPRIL AND HYDROCHLOROTHIAZIDE ACTIVE AGENTS USED IN THE TREATMENT OF HYPERTENSION

Background: Antihypertensive and diuretic drugs are widely used in patients to regulate high blood pressure. Objective of current study was to prepare various cilazapril and hydrochlorothiazide mixtures, to create a matrix effect in the drug and to determine the determination of these active substances in drug samples after optimum conditions. Method: In the spectrophotometric method, 100 mgL−1 solutions were prepared in cilazapril, hydrochlorothiazide in methanol + 0.1 m HCL solvent and then mixtures of these solutions were prepared between specific ppm. The absorbance’s of the solvent against the blind were read at 0.1 nm intervals. After the mixture, tablet (drug) sample was prepared and chemometrics methods were applied to the values obtained by saving the absorbance values. Results: It was observed that the main component analysis applied as a result of spectrophotometric determination of various mixtures of cilazapril and hydrochlorothiazide used in the study gave correct results. These results were validated using various chemometric parameters. Conclusion: The proposed chemometric method can be used in routine analysis in industrial laboratories. Peer Review History: Received 7 November 2020; Revised 8 Decembe; Accepted 4 January, Available online 15 January 2021 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Comments of reviewer(s): Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Ali Abdullah Al-yahawi, Al-Razi university, Department of Pharmacy, Yemen, [email protected] Dr. U. S. Mahadeva Rao, Universiti Sultan Zainal Abidin, Terengganu Malaysia, [email protected] Similar Articles: VALIDATION OF HPLC AND UV VISIBLE METHODS FOR FEW SELECTED BLOOD PRESSURE LOWERING DRUGS AND THEIR FORMULATIONS

Spectroelectrochemical Determination of Isoprenaline in a Pharmaceutical Sample

UV/Vis absorption spectroelectrochemistry (SEC) is a multi-response technique that has been commonly used for the characterization of materials and the study of reaction mechanisms. However, it has been scarcely used for quantitative purposes. SEC allows us to obtain two analytical signals simultaneously, yielding a dual sensor in just one experiment. In the last years, our group has developed new devices useful for analysis. In this work, a SEC device in parallel configuration, based on optical fibers fixed on screen-printed electrodes, was used to determine isoprenaline in a commercial drug, using both, the electrochemical and the spectroscopic signals. In this commercial drug, isoprenaline is accompanied in solution by other compounds. Among them is sodium metabisulfite, an antioxidant that strongly interferes in the isoprenaline determination. A simple pretreatment of the drug sample by bubbling wet-air allows us to avoid the interference of metabisulfite. Here, we demonstrate again the capabilities of UV/Vis absorption SEC as double sensor for analysis and we propose a simple pretreatment to remove interfering compounds.

Piloting the UK’s First Home-Office-Licensed Pharmacist-Led Drug Checking Service at a Community Substance Misuse Service

(1) Introduction: Drug-related deaths in the UK are at concerning high levels. The unknown content and purity of illicit substances can cause unpredictable adverse effects and thus a public health risk with no sign of abating. On-site drug checking is a public health strategy that has previously been implemented, predominantly in festival settings, but without Home Office licensing. (2) Aims: The aim of this study was to pilot the UK’s first pharmacist-led, Home Office-licensed community drug checking service. (3) Methods: A bespoke protocol incorporating legally, professionally and ethically binding documents was implemented. This free, confidential service ran between February and March 2019, was available to anyone over 18 who were purposefully recruited, gave informed consent and agreed to relinquish their drug sample. Samples were checked on-site within an established Substance Misuse Service (SMS) using a handheld Raman spectrometer to determine likely drug content and adulterants. In parallel, participants completed a questionnaire about their substance use and the drug sample(s) being tested. A pharmacist-led multidisciplinary approach was adopted to discuss the analytical findings. Informed by the results of the analysis and the questionnaire, people who used the service received tailored harm reduction advice. (4) Results and Discussion: The pilot operated for a total of four days over four weeks. Eleven people visited and relinquished a total of thirteen samples. Half of the participants had previously overdosed and were known to the SMS. Seventy per cent were male, all were White British individuals, 30% were employed and two people disclosed visiting from another nearby town. Samples included what was thought to be heroin, synthetic cannabinoids, stimulants, benzodiazepines and LSD and none required activation of the “alerts cascade” process. Most participants drank alcohol regularly and the concomitant use of traditional illicit drugs and prescribed medication (including opioids, anxiolytics and antidepressants) with sedating profiles was common. Given some of the ethical decisions and interpretation of the results, specialist pharmacist involvement was deemed essential. (5) Conclusions: This pilot demonstrated the proof-of-concept that a pharmacist-led Home Office-licensed drug checking service can be successfully implemented in community SMSs.

ESTIMATION OF ONDANSETRON HYDROCHLORIDE BY RP-HPLC

A RP-HPLC method was developed for the estimation of Ondansetron Hydrochloride in Bulk drug using high performance liquid chromatography. Ondansetron was a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic drug to treat nausea and vomiting after cancer chemotherapy. The separation was achieved by Promosil C-18 (250 mm x 4.6 mm x 10 µm) column because it allows higher separation and Acetonitrile: Methanol (50:50) as mobile phase with a flow rate of 1.2 ml/min. The detection was carried out at 216 nm. The retention time of drug was found 2.64 min. The developed method was validated. The proposed method shall prove equally effective to analyze Ondansetron Hydrochloride in the corresponding drug sample and may prove to be of great importance in pharmaceutical analysis. KEYWORDS: Ondansetron, Acetonitrile, Antiemetic, Methanol.

Effect of Carbonate Hydroxyapatite (CHA) on the Properties of Pectin Edible Films

Pectin is a derivative polysaccharides biopolymer that can be used as a material for an edible film. In this study, pectin edible film was made from a thin layer of edible pectin. The physical properties of the edible films such as elongation of the break, tensile strength, and the swelling degree were observed when carbonate hydroxyapatite (CHA) was added to the pectin edible film. In order to study the loading and release behavior of the pectin edible film, cinnamaldehyde (2 wt%) was also added to the film used as a drug sample. Cinnamaldehyde is known as a derivative compound of cinnamon bark. The edible film was made by mixing pectin (0.015 g/mL) and carbonate hydroxyapatite (CHA). Various concentration of carbonate hydroxyapatite (1, 3, 5, 7 wt%) was diluted in water and stirred using tween 80 and glycerol for about 1.5 h at a temperature of 70 °C. Then, cinnamaldehyde was added to the mixture and stirred for 30 minutes. The mixture was dried in an oven at a temperature of 50 °C for 15 h and stored in the desiccator. The experiment results showed that the tensile strength of pectin edible film was increased when more concentration of CHA added to the film, but the elongation of break and swelling were decreased. These results indicate that the addition of carbonate hydroxyapatite (CHA) affects the properties of pectin edible film significantly but does not affect the thickness of the film.