The effect of COVID-19 home quarantine on the psychological state of pharmacy students: a cross-sectional study.

BACKGROUND: Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. METHODS: A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. RESULTS: A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. CONCLUSIONS: Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem.

HPLC Method for Simultaneous Determination of Bisphenol-A-Diglycidyl Ether and Some of Its Reaction Products in Canned Foods Using Photodiode Array Detector.

Gradient reversed-phase high-performance liquid chromatography with photodiode array detection was used for separation, detection and quantification of bisphenol-A-diglycidyl ether (BADGE) and some of its reaction products, namely, BADGE·HCl·H2O, BADGE·H2O and BADGE·2HCl in pure form and in canned foods, where canned beans and tuna were used as representatives of aqueous and oil-in-water food matrices, respectively. The proposed method had a linear range of 0.01-0.5 µg g-1 for BADGE·HCl·H2O, BADGE·H2O, BADGE·2HCl and 0.02-0.7 µg g-1 for BADGE in aqueous food matrices. In oil-in-water matrices, the method was proven to be sensitive over a linear range of 0.01-0.5 µg g-1 for BADGE·HCl·H2O, BADGE·H2O and 0.02-0.7 µg g-1 for BADGE·2HCl and BADGE. The limits of detection and quantification ranged from 0.24 to 1.22 ng g-1 and 0.73 to 14.07 ng g-1, respectively. Excellent intraday and interday precision (n = 9) were obtained with RSD% of 0.84-2.19% and 1.88-2.52%, respectively. Accuracy was measured at five concentration levels and the recoveries ranged from 96.31% to 98.76% with an acceptable variation of ±0.9-2.87. Results suggest that the proposed method could be applied for the routine analysis of the studied compounds in their laboratory-prepared mixtures and in various types of canned foods following the limits and regulations of the European Union.

Application of a Fast Separation Method for Anti-diabetics in Pharmaceuticals Using Monolithic Column: Comparative Study With Silica Based C-18 Particle Packed Column.

Run time is a predominant factor in HPLC for quality control laboratories especially if there is large number of samples have to be analyzed. Working at high flow rates cannot be attained with silica based particle packed column due to elevated backpressure issues. The use of monolithic column as an alternative to traditional C-18 column was tested for fast separation of pharmaceuticals, where the results were very competitive. The performance comparison of both columns was tested for separation of anti-diabetic combination containing Metformin, Pioglitazone and Glimepiride using Gliclazide as an internal standard. Working at high flow rates with less significant backpressure was obtained with the monolithic column where the run time was reduced from 6 min in traditional column to only 1 min in monolithic column with accepted resolution. The structure of the monolith contains many pores which can adapt the high flow rate of the mobile phase. Moreover, peak symmetry and equilibration time were more efficient with monolithic column.

Comparative Study Between Multivariate and Univariate Analysis of Two Antidiabetic Combinations.

New multivariate and univariate methods were developed for the analysis of two novel gliptin combinations by manipulating the zero-order and ratio spectra of empagliflozin and linagliptin in combination, with application on Glyxambi® tablets, and of alogliptin and pioglitazone in combination, with application on Oseni® tablets. Linearity ranges for chemometric approaches using principal component regression and partial least-squares were found to be 2-10, 2.5-12.5, 5-15, and 5-25 µg/mL for empagliflozin, linagliptin, alogliptin, and pioglitazone, respectively, whereas the respective linearity ranges for the spectrophotometric approaches were found to be 5-15, 2-12, 5-15, and 5-15 µg/mL. The proposed spectrophotometric methods included ratio subtraction coupled with extended ratio subtraction, spectrum subtraction coupled with constant multiplication, and mean centering. Acceptable LOD and LOQ values were obtained by all methods. Statistical analysis showed no significant difference between multivariate and univariate methods in comparison with the reference methods. The optimized methods provide fast and economic determination of the recently approved antidiabetic combinations without the complex instrumentation or time-consuming mobile phase preparations that were used in the chromatographic techniques reported in the literature.

Comparative Study of Univariate Spectrophotometry and Multivariate Calibration for the Determination of Levamisole Hydrochloride and Closantel Sodium in a Binary Mixture.

Six simple, accurate, reproducible, and selective derivative spectrophotometric and chemometric methods have been developed and validated for the determination of levamisole HCl (Lev) either alone or in combination with closantel sodium (Clo) in the pharmaceutical dosage form. Lev was determined by first-derivative, first-derivative ratio, and mean-centering methods by measuring the peak amplitude at 220.8, 243.8, and 210.4 nm, respectively. The methods were linear over the concentration range 2.0-10.0 µg/mL Lev. The methods exhibited a high accuracy, with recovery data within ±1.9% and RSD <1.3% (n = 9) for the determination of Lev in the presence of Clo. Fortunately, Lev showed no significant UV absorbance at 370.6 nm, which allowed the determination of Clo over the concentration range 16.0-80.0 µg/mL using zero-order spectra, with a high precision (RSD <1.5%, n = 9). Furthermore, principal component regression and partial least-squares with optimized parameters were used for the determination of Lev in the presence of Clo. The recovery was within ±1%, with RSD <1.0% (n = 9) and root mean square error of prediction ≤1.0. The proposed methods were validated according to the International Conference on Harmonization guidelines. The proposed methods were used in the determination of Lev and Clo in a binary mixture and a pharmaceutical formulation, with high accuracy and precision.

Spectrophotometric and chemometric methods for determination of imipenem, ciprofloxacin hydrochloride, dexamethasone sodium phosphate, paracetamol and cilastatin sodium in human urine.

New accurate, sensitive and selective spectrophotometric and chemometric methods were developed and subsequently validated for determination of Imipenem (IMP), ciprofloxacin hydrochloride (CIPRO), dexamethasone sodium phosphate (DEX), paracetamol (PAR) and cilastatin sodium (CIL) in human urine. These methods include a new derivative ratio method, namely extended derivative ratio (EDR), principal component regression (PCR) and partial least-squares (PLS) methods. A novel EDR method was developed for the determination of these drugs, where each component in the mixture was determined by using a mixture of the other four components as divisor. Peak amplitudes were recorded at 293.0 nm, 284.0 nm, 276.0 nm, 257.0 nm and 221.0 nm within linear concentration ranges 3.00-45.00, 1.00-15.00, 4.00-40.00, 1.50-25.00 and 4.00-50.00 µg mL(-1) for IMP, CIPRO, DEX, PAR and CIL, respectively. PCR and PLS-2 models were established for simultaneous determination of the studied drugs in the range of 3.00-15.00, 1.00-13.00, 4.00-12.00, 1.50-9.50, and 4.00-12.00 µg mL(-1) for IMP, CIPRO, DEX, PAR and CIL, respectively, by using eighteen mixtures as calibration set and seven mixtures as validation set. The suggested methods were validated according to the International Conference of Harmonization (ICH) guidelines and the results revealed that they were accurate, precise and reproducible. The obtained results were statistically compared with those of the published methods and there was no significant difference.

Simultaneous Determination of Octinoxate, Oxybenzone, and Octocrylene in a Sunscreen Formulation Using Validated Spectrophotometric and Chemometric Methods.

Accurate, reliable, and sensitive spectrophotometric and chemometric methods were developed for simultaneous determination of octinoxate (OMC), oxybenzone (OXY), and octocrylene (OCR) in a sunscreen formulation without prior separation steps, including derivative ratio spectra zero crossing (DRSZ), double divisor ratio spectra derivative (DDRD), mean centering ratio spectra (MCR), and partial least squares (PLS-2). With the DRSZ technique, the UV filters could be determined in the ranges of 0.5-13.0, 0.3-9.0, and 0.5-9.0 µg/mL at 265.2, 246.6, and 261.8 nm, respectively. By utilizing the DDRD technique, UV filters could be determined in the above ranges at 237.8, 241.0, and 254.2 nm, respectively. With the MCR technique, the UV filters could be determined in the above ranges at 381.7, 383.2, and 355.6 nm, respectively. The PLS-2 technique successfully quantified the examined UV filters in the ranges of 0.5-9.3, 0.3-7.1, and 0.5-6.9 µg/mL, respectively. All the methods were validated according to the International Conference on Harmonization guidelines and successfully applied to determine the UV filters in pure form, laboratory-prepared mixtures, and a sunscreen formulation. The obtained results were statistically compared with reference and reported methods of analysis for OXY, OMC, and OCR, and there were no significant differences with respect to accuracy and precision of the adopted techniques.

Validation of four different spectrophotometric methods for simultaneous determination of Domperidone and Ranitidine in bulk and pharmaceutical formulation.

Four simple, specific, accurate and precise spectrophotometric methods were developed and validated for simultaneous determination of Domperidone (DP) and Ranitidine Hydrochloride (RT) in bulk powder and pharmaceutical formulation. The first method was simultaneous ratio subtraction (SRS), the second was ratio subtraction (RS) coupled with zero order spectrophotometry (D(0)), the third was first derivative of the ratio spectra ((1)DD) and the fourth method was mean centering of ratio spectra (MCR). The calibration curve is linear over the concentration range of 0.5-5 and 1-45 µg mL(-1) for DP and RT, respectively. The proposed spectrophotometric methods can analyze both drugs without any prior separation steps. The selectivity of the adopted methods was tested by analyzing synthetic mixtures of the investigated drugs, also in their pharmaceutical formulation. The suggested methods were validated according to International Conference of Harmonization (ICH) guidelines and the results revealed that; they were precise and reproducible. All the obtained results were statistically compared with those of the reported method, where there was no significant difference.

Screening and Optimization of the Reaction of Polymyxin B Sulphate with NBD-Cl for the Synchronous Spectrofluorimetric Determination of Polymyxin B Sulphate in Human Plasma.

An accurate and sensitive synchronous spectrofluorimetric method has been developed for the determination of Polymyxin B sulphate (Poly B) in human plasma. The method is based on the reaction of non-fluorescent Poly B with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7 producing a yellow color with maximum relative fluorescence at 440 nm using a constant wavelength difference Δλ = 80 nm. Reaction conditions and other analytical parameters were studied and optimized using factorial design. Three level factorial designs have been employed for the screening, optimization of all experimental variables and determination of their interactions on the final product formation. The variables under investigation were: pH of borate buffer, volume of buffer, volume of NBD-Cl, temperature, time of heating and volume of sulfuric acid. A linear plot between relative fluorescence and concentration was obtained over the concentration range 100.00-1200.00 ng mL(-1). The limit of detection (LOD) and limit of quantification (LOQ) were found to be 10.31 and 31.24 ng mL(-1), respectively. The proposed method was validated according to ICH guidelines and successfully applied for the determination of Poly B in human plasma, where satisfactory results were obtained. The results obtained were statistically compared with those of a published method, where no significant difference was observed.

Application of Savitzky-Golay differentiation filters and Fourier functions to simultaneous determination of cefepime and the co-administered drug, levofloxacin, in spiked human plasma.

The present work is concerned with simultaneous determination of cefepime (CEF) and the co-administered drug, levofloxacin (LEV), in spiked human plasma by applying a new approach, Savitzky-Golay differentiation filters, and combined trigonometric Fourier functions to their ratio spectra. The different parameters associated with the calculation of Savitzky-Golay and Fourier coefficients were optimized. The proposed methods were validated and applied for determination of the two drugs in laboratory prepared mixtures and spiked human plasma. The results were statistically compared with reported HPLC methods and were found accurate and precise.

Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments.

Simple, selective and reproducible spectrofluorimetric and spectrophotometric methods have been developed for the determination of vildagliptin and saxagliptin in bulk and their pharmaceutical dosage forms. The first proposed spectrofluorimetric method is based on the dansylation reaction of the amino group of vildagliptin with dansyl chloride to form a highly fluorescent product. The formed product was measured spectrofluorimetrically at 455 nm after excitation at 345 nm. Beer's law was obeyed in a concentration range of 100-600 µg ml(-1). The second proposed spectrophotometric method is based on the charge transfer complex of saxagliptin with tetrachloro-1,4-benzoquinone (p-chloranil). The formed charge transfer complex was measured spectrophotometrically at 530 nm. Beer's law was obeyed in a concentration range of 100-850 µg ml(-1). The third proposed spectrophotometric method is based on the condensation reaction of the primary amino group of saxagliptin with formaldehyde and acetyl acetone to form a yellow colored product known as Hantzsch reaction, measured at 342.5 nm. Beer's law was obeyed in a concentration range of 50-300 µg ml(-1). All the variables were studied to optimize the reactions' conditions using factorial design. The developed methods were validated and proved to be specific and accurate for quality control of vildagliptin and saxagliptin in their pharmaceutical dosage forms.

Stability-indicating liquid chromatographic method for determination of saxagliptin and structure elucidation of the major degradation products using LC-MS.

A new, simple, selective, reproducible and sensitive stability-indicating liquid chromatographic method was developed and subsequently validated for the determination of saxagliptin (SXG). SXG was subjected to oxidation, thermal, acid hydrolysis, alkali hydrolysis and photodegradation according to ICH guidelines. The major degradation products were separated from the pure drug and the proposed structures' elucidation was performed, using an LC-MS technique. Isocratic chromatographic elution was achieved on a Symmetry(®) C18 column (150 × 4.6 mm, 5 µm), using a mobile phase of potassium dihydrogen phosphate buffer (pH 4.6)-acetonitrile-methanol (40 : 30 : 30, v/v/v) at a flow rate of 1 mL min(-1) with UV detection at 208 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 25-400 µg mL(-1). All the results were statistically compared with the reference method, using one-way analysis of variance. The developed method was validated and proved to be specific and accurate for quality control of SXG in pharmaceutical dosage form.

Comparative study for determination of some polycyclic aromatic hydrocarbons 'PAHs' by a new spectrophotometric method and multivariate calibration coupled with dispersive liquid-liquid extraction.

A modified dispersive liquid-liquid extraction (DLLE) procedure coupled with spectrophotometric techniques was adopted for simultaneous determination of naphthalene, anthracene, benzo(a)pyrene, alpha-naphthol and beta-naphthol in water samples. Two different methods were used, partial least-squares (PLS) method and a new derivative ratio method, namely extended derivative ratio (EDR). A PLS-2 model was established for simultaneous determination of the studied pollutants in methanol, by using twenty mixtures as calibration set and five mixtures as validation set. Also, in methanol a novel (EDR) method was developed for determination of the studied pollutants, where each component in the mixture of the five PAHs was determined by using a mixture of the other four components as divisor. Chemometric and EDR methods could be also adopted for determination of the studied PAH in water samples after transferring them from aqueous medium to the organic one by utilizing dispersive liquid-liquid extraction technique, where different parameters were investigated using a full factorial design. Both methods were compared and the proposed method was validated according to ICH guidelines and successfully applied to determine these PAHs simultaneously in spiked water samples, where satisfactory results were obtained. All the results obtained agreed with those of published methods, where no significant difference was observed.

Novel spectroscopic methods for determination of Cromolyn sodium and Oxymetazoline hydrochloride in binary mixture.

New accurate, sensitive and selective spectrophotometric and spectrofluorimetric methods were developed and subsequently validated for determination of Cromolyn sodium (CS) and Oxymetazoline HCl (OXY) in binary mixture. These methods include 'H-point standard addition method (HPSAM) and area under the curve (AUC)' spectrophotometric method and first derivative synchronous fluorescence spectroscopic (FDSFS) method. For spectrophotometric methods, absorbances were recorded at 241.5nm and 274.9nm for HPSAM and the wavelength was selected in ranges 232.0-254.0nm and 216.0-229.0nm for AUC method, where the concentration was obtained by applying Cramer's rule. For FDSFS method, the first-derivative synchronous fluorescence signal was measured at 290.0nm, using Δλ=145.0nm. The suggested methods were validated according to International Conference of Harmonization (ICH) guidelines and the results revealed that they were precise and reproducible. All the obtained results were statistically compared with those of the reported method and there was no significant difference.

Novel method for determination of anthracene by coupling dispersive liquid-liquid extraction to first-derivative synchronous spectrofluorimetry.

A novel method could be adopted successfully for determination of anthracene in environmental samples, utilizing dispersive liquid-liquid extraction followed by first-derivative synchronous fluorimetry at a constant wavelength difference Δλ = 165 nm, where a linear calibration curve was obtained in a concentration range of 0.5-100 ng mL(-1) at 244 nm. The detection limit was 0.1 ng mL(-1). The method can be easily adopted for determination of anthracene in aqueous media including tap water and river water. The recoveries obtained were 85.40-108.02%. The proposed method was validated according to International Conference of Harmonization (ICH) guide lines and successfully applied to determine anthracene in pure form and in water samples including real life water samples from different sources. All the results obtained were compared with those of published method, where no a significant difference was observed.

Validation of different spectrophotometric methods for determination of vildagliptin and metformin in binary mixture.

New, simple, specific, accurate, precise and reproducible spectrophotometric methods have been developed and subsequently validated for determination of vildagliptin (VLG) and metformin (MET) in binary mixture. Zero order spectrophotometric method was the first method used for determination of MET in the range of 2-12 µg mL(-1) by measuring the absorbance at 237.6 nm. The second method was derivative spectrophotometric technique; utilized for determination of MET at 247.4 nm, in the range of 1-12 µg mL(-1). Derivative ratio spectrophotometric method was the third technique; used for determination of VLG in the range of 4-24 µg mL(-1) at 265.8 nm. Fourth and fifth methods adopted for determination of VLG in the range of 4-24 µg mL(-1); were ratio subtraction and mean centering spectrophotometric methods, respectively. All the results were statistically compared with the reported methods, using one-way analysis of variance (ANOVA). The developed methods were satisfactorily applied to analysis of the investigated drugs and proved to be specific and accurate for quality control of them in pharmaceutical dosage forms.

Novel Comparative Synchronous Spectrofluorimetric Study of Benzo(a)pyrene Using Beta-Cyclodextrin and Calix(8)arene as Fluorescence Enhancers.

Successfully benzo(a)pyrene could be quantitified in environmental samples by a novel synchronous spectrofluorimetric techniques at a constant wavelength difference Δλ = 120 nm, using beta-cyclodextrin 'ß-CD' and calix(8)arene as fluorescence enhancers, where a linear calibration curve was obtained in a concentration range of 900-14,400 pg mL(-1) and 18-360 pg mL(-1) and the detection limit of 380.00 pg mL(-1) and 12.08 pg mL(-1) (which is well below the maximum contaminant concentration for benzo(a)pyrene set by the Environmental Protection Agency 'EPA') using both enhancers, respectively. The method can be easily adopted for determination of benzo(a)pyrene in aqueous media including tap water, river water and complex water samples. The recoveries obtained were 85.13-113.36 % with RSD < 4 %. The proposed method was validated according to International Conference of Harmonization (ICH) guide lines and successfully applied to determine benzo(a)pyrene in pure form and in water samples including contaminated environmental water samples. All the results obtained were compared with those of a published method, where no significant difference was observed.