Spectrophotometric and Spectrofluorimetric Studies on Azilsartan Medoxomil and Chlorthalidone to Be Utilized in Their Determination in Pharmaceuticals

The recently approved angiotensin II receptor blocker, azilsartan medoxomil (AZL), was determined spectrophotometrically and spectrofluorimetrically in its combination with chlorthalidone (CLT) in their combined dosage form. The UV-spectrophotometric technique depends on simultaneous measurement of the first derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol. The spectrofluorimetric technique depends on measurement of the fourth derivative of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in methanol. The effects of different solvents on spectrophotometric and spectrofluorimetric responses were studied. For, the spectrofluorimetric study, the effect of pH and micelle-assisted fluorescence enhancement were also studied. Linearity, accuracy, and precision were found to be satisfactory over the concentration ranges of 8–50 μg mL-1 and 2–20 μg mL-1 for AZL and CLT, respectively, in the spectrophotometric method as well as 0.01–0.08 μg mL-1 for AZL in the spectrofluorimetric method. The methods were successfully applied for the determination of the studied drugs in their co-formulated tablets. The developed methods are inexpensive and simple for the quality control and routine analysis of the cited drugs in bulk and in pharmaceuticals

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Liquid chromatographic and spectrophotometric methods for the determination of erythromycin stearate and trimethoprim in tablets

Simple, accurate and precise reversed-phase liquid chromatographic (LC) and spectrophotometric methods have been developed and validated for the determination of erythromycin stearate (ERS) and trimethoprim (TMP) in mixture. In LC method, chromatographic separation was achieved on a Symmetry® Waters C18 column (150 × 4.6 mm, 5 μm) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (9):acetonitrile:water (25:100:50, v/v/v) at a flow rate of 1.6 ml min−1 with UV detection at 210 nm for ERS and 280 nm for TMP. Besides, two spectrophotometric methods were applied after reaction with perchloric acid (12 M) which gives a colored product with ERS. Then, the spectral interference between the colored product of ERS and TMP was resolved by either ratio spectra derivative spectrophotometry in the first spectrophotometric method or chemometric techniques, namely classical least-squares (CLS), principal component regression (PCR) and partial least-squares regression (PLS) in the second spectrophotometric method. The results were statistically compared using one-way analysis of variance (ANOVA). The methods developed were satisfactorily applied to the analysis of the pharmaceutical preparation containing the two drugs and proved to be specific and accurate for the quality control of the cited drugs in pharmaceutical dosage forms

Utilizing experimental design and desirability function in optimizing RP-HPLC method for simultaneous determination of some skeletal muscle relaxants and analgesics

Abstract An experimental design and response surface methodologies using Plackett–Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate parameters which significantly affect the separation and quantitative estimation of five skeletal muscle relaxants and four analgesic drugs (baclofen, methocarbamol, dantrolene sodium, orphenadrine citrate, cyclobenzaprine hydrochloride, ketoprofen, etoricoxib, ibuprofen, and mefenamic acid) with a relatively short duration of analysis in a single run. For the separation of the nine drugs, an INERTSIL ODS-V3-5 µm C18 column (250 × 4.6 mm I.D.) was used with the optimum mobile phase conditions (45.15 mM ammonium acetate buffer pH 5.56 adjusted with acetic acid, acetonitrile, and methanol in a ratio of 30.5:29.5:40, v/v/v with a flow rate of 1.5 mL/min) and UV-detection at 220 nm. The optimized method was successfully subjected to the validation steps as described in ICH guidelines for linearity, precision, accuracy, robustness, and sensitivity. The optimized and validated method was effectively applied to determine the content of the studied drugs in their pharmaceutical preparations and to expand its applicability to the counterfeit estimation of etoricoxib in different brands of tablet dosage forms

Validated HPLC and Ultra-HPLC Methods for Determination of Dronedarone and Amiodarone Application for Counterfeit Drug Analysis

Two simple, accurate, and precise chromatographic methods have been developed and validated for the determination of dronedarone (DRO) HCl and amiodarone (AMI) HCl either alone or in binary mixtures due to the possibility of using AMI as a counterfeit of DRO because of its lower price. First, an RP-HPLC method is described for the simultaneous determination of DRO and AMI. Chromatographic separation was achieved on a BDS Hypersil C18 column (150 × 4.6 mm, 5 μm). Isocratic elution based on potassium dihydrogen phosphate buffer with 0.1% triethylamine pH 6–methanol (10 + 90, v/v) at a flow rate of 2 mL/min with UV detection at 254 nm was performed. The second method is RP ultra-HPLC in which the chromatographic separation was achieved on an AcclaimTM RSLC 120 C18 column (100 × 2.1 mm, 2.2 μm) using isocratic elution with potassium dihydrogen phosphate buffer with 0.1% triethylamine pH 6–methanol (5 + 95, v/v) at a flow rate of 1 mL/min with UV detection at 254 nm. Linearity, accuracy, and precision of the two methods were found to be acceptable over the concentration ranges of 5–80 μg/mL for both DRO and AMI. The results were statistically compared using one-way analysis of variance. The optimized methods were validated and proved to be specific, robust, precise, and accurate for the QC of the drugs in their pharmaceutical preparations

Validated Spectrophotometric Methods for Determination of Weakly UV absorbed Perindopril Arginine in Bulk and Combined Dosage Form

Five simple, specific, accurate and precise spectrophotometric methods were developed and validated for the simultaneous determination of the oral antihypertensive drugs; perindopril arginine (PER) and amlodipine besylate (AML) in their combined dosage form. AML can be determined directly by measuring its absorbance at λmax357 nm. On the other hand PER was determined by five different methods. The first two methods, ratio derivative (RD) and Derivative subtraction coupled with the constant multiplication method (DS-CM), were performed using the ratio spectra. While the other three methods, amplitude factor (P-Factor), amplitude subtraction (AS) and modified amplitude subtraction (MAS), were developed based on derivative spectroscopy followed by mathematical manipulation. No preliminary separation steps were required for the proposed spectrophotometric methods. Linearity, accuracy and precision of the method was found to be acceptable over the concentration ranges of 20-80 μg/mL for PER and 5-40 μg/mL for AML. The proposed spectrophotometric methods were statistically compared to that of reference methods using one-way analysis of variance (ANOVA). The results showed that there was no significant difference between them

Application of Box-Behnken design for optimization of an RP-HPLC method for determination of palonosetron and netupitant in their combined dosage form in presence of their impurities

The use of (Netupitant and Palonosetron) combination to treat nausea and vomiting in cancer chemotherapy patients has been authorized by the Food and Drug Administration. For the simultaneous determination of Netupitant (NET) and palonosetron (PAL) in the presence of two of their related substances and in their dosage form, a sensitive and selective RP-HPLC method has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method’s analytical parameters. It employed RP-HPLC with a UV detector. Waters ODS-C18 column (3.5 µm, 75 × 4.6 mm) with a mobile phase composed of acetonitrile: 25 mM phosphate buffer (pH = 3.5) in a gradient mode at 254 nm was employed to separate the cited drugs and their impurities. Palonosetron was linear over the concentration range (1–50 µg/mL) and Netupitant (10–100 µg/mL). According to ICH guidelines, the new method underwent thorough validation. Between the proposed method’s results and those from the reported method, there was no significant difference. It is easy to apply the technique to the analysis of the specified drugs in their combination dosage form for quality control considerations.</p

Analysis and bio-analysis of omarigliptin, trelagliptin and alogliptin: Applied to biological samples and degradation kinetic study

A simple liquid chromatographic method was developed for the bio-assay of omarigliptin (OMR), trelagliptin (TRE) and alogliptin (ALO) in rat plasma using Hypersil Gold C18 column with UV detection as an economic alternative for the reported LC-MS methods in the literature. Isocratic elution based on simple mobile phase (acetonitrile:phosphate buffer, 50:50, v/v) was applied with UV detection at 240 nm for OMR and at 274 nm for TRE and ALO because of their structure similarity except for one fluorine atom. Liquid-liquid extraction technique was used for plasma sample preparations using diethyl ether as the best extracting solvent according to log-P of the drugs & applying vacuum evaporation before the reconstitution with the mobile phase. The method was validated according to FDA guidelines. The proposed method was applied to biological samples (n = 3) after oral administration to rats. Further applications were completed using the same LC method including assay of TRE and ALO in human plasma and study of stress degradation for OMR in bulk as a stability indicating assay. Factorial design was applied to test the method robustness using Box Behnken design with three factors and one replicate. First order kinetic plot of acid degradation of OMR at 60 °C, 70 °C & 80 °C showed kinetic plots of the natural logarithm (Ln) of OMR remaining percent versus time for each temperature. Arrhenius plot was used in the kinetic study and half-life (t1/2), shelf life (t90), degradation rate constant (K25), Activation energy (Ea) & Arrhenius frequency factor (A) were calculated. A minor comparative study was also applied to show the difference between UPLC, UHPLC & HPLC for the assay of OMR. All of these applications were performed with the minimal possible cost as the major privilege of the presented economic work over the reported expensive LC-MS bio-analytical methods