A novel method for tizanidine hydrochloride determination in aqueous solution based on fluorescence quenching of functionalised CdS quantum dots as luminescent probes

A novel, sensitive and convenient method for the determination of tizanidine hydrochloride (TZD) based on the fluorescence quenching of thioglycolic acid-capped CdS quantum dots (TGA-CdS QDs) is proposed. Luminescent CdS semiconductor quantum dots modified by thioglycolic acid were synthesized from cadmium nitrate and sodium sulfide in alkaline aqueous solution. The modified CdS QDs are water-soluble, stable and highly luminescent. When TZD was added into the CdS QDs colloidal solution, the surface of CdS QDs generates the electrostatic interaction in aqueous medium, which induces the quenching of fluorescence emission at 518 nm upon excitation at 340 nm. Under the optimal conditions, the Stern-Volmer calibration plot of F­ο/F against concentration of TZD was linear in the range of 3.0-18.0 μg/mL with a correlation coefficient of 0.9953. The detection limit was 1.35 μg/mL. The relative standard deviation for five determinations of 9 μg/mL TZD was 2.29%. The proposed method was successfully applied to commercial tablets with satisfactory results. The results were found to be in good agreement with those obtained by the reference method. The possible fluorescence quenching mechanism for the reaction is also discussed

Development and validation of a reversed phase liquid chromatographic method for the determination of three Gliptins and Metformin in the presence of Metformin impurity (1-cyanoguanidine)

A simple and precise liquid chromatographic method has been developed and validated for the determination of either sitagliptin (STG), vildagliptin (VLG) or saxagliptin HCL (SXG) and metformin HCL (MET) in the presence of metformin degradation product, 1-cyanoguanidine (CGN). Chromatographic separation was achieved on a Symmetry® cyanide column (150 mm × 4.6 mm, 5 μm). Isocratic elution using a mobile phase of potassium dihydrogen phosphate buffer (pH = 4.6) - acetonitrile (30:70, v:v) at a flow rate of 1 mL/min with UV detection at 210 nm was performed. The LC method was used for the simultaneous determination of STG, VLG, SXG and MET in the ranges of 5-200, 5-200, 0.5-80.0 and 20-800 μg/mL, respectively. The results were statistically compared with the reference method for each drug using one-way analysis of variance (ANOVA). The method developed was satisfactorily applied to the analysis of the pharmaceutical formulations and proved to be specific and accurate for the quality control of the cited drugs in pharmaceutical dosage forms

Spectrofluorometric determination of linagliptin in bulk and in pharmaceutical dosage form

Simple and precise spectrofluorometric method has been developed and validated for the determination of linagliptin (LNG) in the range of 10-110 μg/mL. The results obtained were of good precision and statistically compared to the reference method using one-way analysis of variance (ANOVA). The method developed was satisfactorily applied to the analysis of the pharmaceutical formulation and proved to be specific and accurate for the quality control of linagliptin in its pharmaceutical dosage form. The development of spectrofluorometric method for the determination of LNG was of interest as no such methods have been reported

Development and validation of a reversed-phase column liquid chromatographic method for simultaneous determination of two novel gliptins in their binary mixtures with Metformin

A new, simple, accurate, and precise liquid chromatographic method has been developed and validated for the determination of two novel dipeptidylpeptidase-4 (DPP-4) inhibitors; namely vildagliptin (VLG) and saxagliptin HCl (SXG) simultaneously in their binary mixtures with metformin HCl (MET). Chromatographic separation was achieved on an Inertsil® CN-3 column (250 mm x 4.6 mm, 5 µm). Isocratic elution using a mobile phase of potassium dihydrogen phosphate buffer pH (4.6) - acetonitrile (15:85, v:v) at a flow rate of 1 mL/min with UV detection at 208 nm was performed. The liquid chromatographic method was used for the simultaneous determination of either VLG, SXG and MET in the range of 5-200, 0.5-20 and 50-2000 μg/mL, respectively. The methods developed were satisfactorily applied to the analysis of the pharmaceutical formulations and proved to be specific and accurate for the quality control of the cited drugs in pharmaceutical dosage forms

Simultaneous determination of sitagliptin and metformin in ternary mixture with sitagliptin acid degradation product

In this work, the acidic degradation product of sitagliptin phosphate monohydrate (STG) was synthesized, separated and its structure was elucidated. Additionally, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of STG. The first method comprised the determination of STG in binary mixture with sitagliptin acid degradation product (SDP) in laboratory prepared mixtures, in plasma and in dosage form. This method was based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer (pH =4.6) - acetonitrile (30:70, v:v) with fluorometric detection. The fluorometric detector was operated at 267 nm for excitation and 575 nm for emission. In the second method, the simultaneous determination of STG and metformin (MET) in the presence of SDP has been developed. In this method, the ternary mixture of STG, MET and SDP was separated using a mobile phase consisting of potassium dihydrogen phosphate buffer (pH = 4.6) - acetonitrile (15:85, v:v) with UV detection at 220 nm. Chromatographic separation in the two methods was achieved on a Symmetry® Waters C18 column (150 mm × 4.6 mm, 5 μm). The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparations

Spectrophotometric methods for the simultaneous determination of paracetamol and dantrolene sodium in pharmaceutical dosage form

Accurate, precise and simple spectrophotometric methods have been developed and validated for the determination of paracetamol (PAR) and dantrolene sodium (DAS). Spectrophotometric methods including zero order, first derivative (1D) and derivative ratio methods (1DD) have been developed. The zero order spectrophotometric method was used for the determination of DAS in the range of 1-20 μg/mL by measuring the absorbance at 379 nm where PAR exhibits zero reading. 1D and 1DD methods were used for the determination of PAR in the range of 1.5-20.0 μg/mL by measuring the peaks amplitudes at 265.5 nm and 265.0 nm, respectively. The proposed methods were used to determine PAR in binary mixture with DAS in the laboratory prepared mixtures and in pharmaceutical dosage form. The results obtained were statistically evaluated and found to be accurate and precise and can be satisfactorily applied for the quality control analysis of the cited drugs

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

Improved reversed phase liquid chromatographic method with pulsed electrochemical detection for tobramycin in bulk and pharmaceutical formulation

Tobramycin is one of the aminoglycoside antibiotics that lack a UV absorbing chromophore. However, the application of pulsed electrochemical detection (PED) has been used successfully for the analysis of this and similar antibiotics. This work describes an improved liquid chromatographic (LC) method combined with PED, which is able to separate much more impurities than before. Using a Discovery C-18 RP column (250mmÃ4.6mm i.d., 5μm), isocratic elution was carried out with a mobile phase, containing sodium sulfate (35g/L), sodium octanesulphonic acid (1g/L), tetrahydrofuran (14mL/L) and 0.2M phosphate buffer pH 3.0 (50mL/L). Using these experimental conditions, the limit of quantification (LOQ, S/N=10) was 5ng. The linearity was examined in the range LOQ-60μg/mL and the coefficient of determination was 0.998. The method also proved to be repeatable and the recovery was close to 100%. The influence of the different chromatographic parameters on the separation was investigated by means of an experimental design. The proposed method is useful in quality control of tobramycin drug substances and drug products. Keywords: Liquid chromatography-Pulsed electrochemical detection, Tobramycin, Aminoglycoside antibiotic

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