Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Monitoring of the degradation kinetics of diatrizoate sodium to its cytotoxic degradant using a stability-indicating high-performance liquid chromatographic method.

The X-ray diagnostic agent sodium diatrizoate (DTA) was studied for chemical degradation. The 3,5-diamino derivative was found to be the alkaline and acidic degradation product. The 3,5-diamino degradate is also the synthetic precursor of DTA and it is proved to have cytotoxic and mutagenic effects. A sensitive, selective and precise high-performance liquid chromatographic stability-indicating method for the determination of DTA in the presence of its acidic degradation product and in pharmaceutical formulation was developed and validated. Owing to the high toxicity of the degradation product, the kinetics of the acidic degradation process was monitored by the developed RP-HPLC method. The reaction was found to follow pseudo-first order kinetics. The kinetic parameters such as rate constant (K) and half-life (t½ ) were calculated under different temperatures and acid concentrations; activation energy was estimated from the Arrhenius plot. The developed RP-HPLC method depends on isocratic elution of a mobile phase composed of methanol-water (25:75 v/v; pH adjusted with phosphoric acid), and UV detection at 238 nm. The method showed good linearity over a concentration range of 2-100 µg/mL with mean percentage recovery of 100.04 ± 1.07. The selectivity of the proposed method was tested using laboratory-prepared mixtures. The proposed method has been successfully applied to the analysis of DTA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with the official USP method. Validation of the proposed method was performed according to International Conference on Harmonization guidelines.

Profiling of esterified fatty acids as biomarkers in the blood of dengue fever patients using a microliter-scale extraction followed by gas chromatography and mass spectrometry.

An improved gas chromatography with mass spectrometry procedure was developed to highlight the esterified fatty acids in 100 µL blood of dengue fever patients in the early febrile phase versus healthy volunteers. 24 adult patients and 24 healthy volunteers were included in this study. The recoveries of targeted esterified fatty acids content were in the range of 92.10-101.00% using methanol/dichloromethane (2:1, v/v) as the extraction solvent. An efficient chromatographic separation of targeted 17 esterified fatty acid methyl esters was obtained. The limits of detection and quantification were within the range of 16-131 and 53-430 ng/mL, respectively. The relative standard deviation of intraday and interday precision values ranged from 0.4 to 5.0%. The statistical data treatment showed a significant decrease of the content of four saturated fatty acids, C14:0, C15:0, C16:0, and C18:0 (P value < 0.05), and also showed a decrease of the content of eight unsaturated fatty acids, C16:1, C18:3n6, C18:2n6, C18:1n9, C20:3n3, C20:4n6, C20:2, and C22:6n3 (P value < 0.05) in dengue fever patients. Moreover, the amount of three omega-6 fatty acids including C18:3n6, C18:2n6, and C20:4n6 was dramatically decreased in the blood of dengue fever patients to a limit of 50 ± 10%.

The Effect of the COVID-19 Pandemic on Academic Research Gender Disparities in Radiology.

RATIONALE AND OBJECTIVES: Gender disparities have long existed in radiology. The COVID-19 pandemic disrupted research activities worldwide and have impacted gender disparities across medical specialties. This study investigates the effect of the COVID-19 pandemic on gender disparities in radiology academic authorship. MATERIALS AND METHODS: A retrospective observational study was conducted using data from 110 843 global and 23 977 US radiology articles. The gender of authors was determined using an automated gender inference tool. Descriptive statistics were applied to explore authorship changes overall globally, in the US as well as across countries and states. RESULTS: Female first-authorship increased globally from 16.9% to 17.6% (p < 0.001), and in the US, from 19.0% to 19.6% (p = 0.19) in the peri-COVID period. The combined female percentage increased from 19.7% to 20.0% globally (p = 0.021), and from 20.2% to 21.1% in the US (p = 0.006). Country-level analysis revealed significant increases in female authorship in Colombia, Denmark, Egypt, France, India, and Japan, while New Zealand demonstrated a decrease in female authorship. In the US, Florida, Indiana, Louisiana, Massachusetts, and Ohio experienced increases in female authorship, whereas South Carolina demonstrated a decrease in female authorship. CONCLUSION: In contrast with other medical fields, the study demonstrates that radiology experienced a slight increase in female authorship in radiology research globally and in the US during the COVID period. While the pandemic may have influenced these findings, further research is needed to establish regional causal relationships and identify best practices for promoting gender equity in radiology research.

Metabolic syndrome: imaging features and clinical outcomes.

Metabolic syndrome, which affects around a quarter of adults worldwide, is a group of metabolic abnormalities characterized mainly by insulin resistance and central adiposity. It is strongly correlated with cardiovascular and all-cause mortality. Early identification of the changes induced by metabolic syndrome in target organs and timely intervention (eg, weight reduction) can decrease morbidity and mortality. Imaging can monitor the main components of metabolic syndrome and identify early the development and progression of its sequelae in various organs. In this review, we discuss the imaging features across different modalities that can be used to evaluate changes due to metabolic syndrome, including fatty deposition in different organs, arterial stiffening, liver fibrosis, and cardiac dysfunction. Radiologists can play a vital role in recognizing and following these target organ injuries, which in turn can motivate lifestyle modification and therapeutic intervention.

Impact analysis of primary and secondary research in radiology journals.

INTRODUCTION: Primary and secondary studies are considered the two major research categories. In this study, we examined the scientific and social media impact of primary and secondary publication types in papers published radiological journals during 2010-2020. MATERIALS AND METHODS: PubMed publication type tags were used to filter original articles and systematic review and meta-analysis (SR/MA) articles. Clarivate Web of Science was utilized to obtain a list of all radiology journals from the category "Radiology, Nuclear Medicine and Imaging" in Science Citation Index Expanded (SCIE). Automated approach was developed for programmatic extraction of bibliometric and Altmetric yearly citations of each included article using Dimensions API and Altmetric API with Python. Statistical analysis was performed to compare the citation rates between primary and secondary research articles. RESULTS: A total of 96,684 published articles from 2010 to 2020 were identified and their meta-data collected. The mean 2-year citation count following publication year was 5.8 for primary research and 10.2 for SR/MA articles (p < 0.001). Between 2010 and 2020, the mean number of citations per SR/MA article was 51.3 compared to 30.5 per primary research article (p < 0.001). Mean Altmetric score was 8.2 in SR/MA compared to 3.7 for primary research articles (p < 0.001). CONCLUSION: Secondary research studies have been increasing in impact in both academia and social media compared to primary research. Our results highlight the importance and impact of systematic reviews and meta-analysis articles as a scientifically influential study type in radiology.

Renal bleeding: imaging and interventions in patients with tumors.

In patients with cancer, spontaneous renal bleeding can stem from a range of underlying factors, necessitating precise diagnostic tools for effective patient management. Benign and malignant renal tumors are among the primary culprits, with angiomyolipomas and renal cell carcinomas being the most common among them. Vascular anomalies, infections, ureteral obstructions, and coagulation disorders can also contribute to renal-related bleeding. Cross-sectional imaging techniques, particularly ultrasound and computed tomography (CT), play pivotal roles in the initial detection of renal bleeding. Magnetic resonance imaging and CT are preferred for follow-up evaluations and aid in detecting underlying enhancing masses. IV contrast-enhanced ultrasound can provide additional information for active bleeding detection and differentiation. This review article explores specific disorders associated with or resembling spontaneous acute renal bleeding in patients with renal tumors; it focuses on the significance of advanced imaging techniques in accurately identifying and characterizing renal bleeding in these individuals. It also provides insights into the clinical presentations, imaging findings, and treatment options for various causes of renal bleeding, aiming to enhance the understanding, diagnosis, and management of the issue.

Long-term outcomes of flow diversion for unruptured intracranial aneurysms: a systematic review and meta-analysis.

BACKGROUND: Flow diverters have been widely used in clinical practice for more than a decade. However, most outcome data are limited to 1 year timepoints. This study aims to offer meta-analysis data on long-term (>1 year) safety and effectiveness results for patients with aneurysms treated with flow diverters. METHODS: PubMed, Web of Science, Embase, and SCOPUS were searched up to February 24, 2022 using the AutoLit platform. We included primary studies assessing the long-term outcomes for flow diverter devices to manage unruptured internal carotid artery aneurysms with a follow-up period of >1 year. The meta-analysis was carried out using Comprehensive Meta-Analysis software (CMA). RESULTS: Eleven studies were included in the meta-analysis. The pooled occlusion rates after flow diversion treatment for unruptured intracranial brain aneurysms were 77%, 87.4%, 84.5%, 89.4%, 96% for 1 year, 1-2 years, 2 years, 3 years, and 5 years follow-up, respectively. The in-stent stenosis rate was 4.8% and the retreatment rate for the long-term follow-up period was 5%. No delayed rupture of the aneurysm was reported, and there was one case of delayed ischemic stroke. The sensitivity analysis of the prospective studies showed a complete occlusion rate of 83.5% and 85.2% for 1 and 3 years of follow-up, respectively. CONCLUSION: Flow diverters are safe and effective in short- and long-term follow-up and rarely cause serious delayed side effects.

Operator assessment versus core laboratory adjudication of recanalization following endovascular treatment of acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Successful recanalization after endovascular thrombectomy serves as the primary endpoint in clinical trials and is a crucial predictor of long-term outcomes. Radiographic outcomes for various interventions have been shown to vary based on the type of interpreter, including the site interventionalist compared with an independent reader. OBJECTIVE: To compare angiographic outcomes in stroke thrombectomy procedures based on the type of reader. METHODS: A systematic literature search was conducted in Medline, EMBASE, Scopus, and Web-of-Science through February 2022. We included primary studies that reported core laboratory-read and operator angiographic outcomes after mechanical thrombectomy for ischemic stroke. Furthermore, study-defined successful recanalization data were collected. RESULTS: Eight studies were included with 4797 patients, 51.2% of whom were male. Four thousand, four hundred and thirty-one patients had core readings, and 4211 had operator readings. Study-defined successful recanalization was significantly higher for operator (84%, 3543/4211) examinations than for core laboratory-read (78.4%, 3476/4431) examinations (p<0.001; OR=1.462, 95% CI 1.175 to 1.819). The modified Thrombolysis in Cerebral Infarction (mTICI) scale score of ≥2 b was higher for operator (85%, 3341/3929) examinations than for core laboratory-read (78.6%, 3107/3952) examinations (p<0.001; OR=1.349, 95% CI 1.071 to 1.701). mTICI 3 was significantly higher for operator (54.6%, 1000/1832) examinations than for core laboratory-read (39.9%, 731/1832) examinations (p<0.001; OR=1.823, 95% CI 1.598 to 2.081). CONCLUSION: Operator angiographic reads are statistically significantly higher than core laboratory-read readings following stroke thrombectomy, especially for complete recanalization. These differences should be considered when interpreting reports of angiographic outcomes after thrombectomy.

Deep-learning CT reconstruction in clinical scans of the abdomen: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic literature review and meta-analysis of the two most common commercially available deep-learning algorithms for CT. METHODS: We used PubMed, Scopus, Embase, and Web of Science to conduct systematic searches for studies assessing the most common commercially available deep-learning CT reconstruction algorithms: True Fidelity (TF) and Advanced intelligent Clear-IQ Engine (AiCE) in the abdomen of human participants since only these two algorithms currently have adequate published data for robust systematic analysis. RESULTS: Forty-four articles fulfilled inclusion criteria. 32 studies evaluated TF and 12 studies assessed AiCE. DLR algorithms produced images with significantly less noise (22-57.3% less than IR) but preserved a desirable noise texture with increased contrast-to-noise ratios and improved lesion detectability on conventional CT. These improvements with DLR were similarly noted in dual-energy CT which was only assessed for a single vendor. Reported radiation reduction potential was 35.1-78.5%. Nine studies assessed observer performance with the two dedicated liver lesion studies being performed on the same vendor reconstruction (TF). These two studies indicate preserved low contrast liver lesion detection (> 5 mm) at CTDIvol 6.8 mGy (BMI 23.5 kg/m2) to 12.2 mGy (BMI 29 kg/m2). If smaller lesion detection and improved lesion characterization is needed, a CTDIvol of 13.6-34.9 mGy is needed in a normal weight to obese population. Mild signal loss and blurring have been reported at high DLR reconstruction strengths. CONCLUSION: Deep learning reconstructions significantly improve image quality in CT of the abdomen. Assessment of other dose levels and clinical indications is needed. Careful choice of radiation dose levels is necessary, particularly for small liver lesion assessment.

Perirenal lymphatics: anatomy, pathophysiology, and imaging spectrum of diseases.

Despite being rarely discussed, perinephric lymphatics are involved in many pathological and benign processes. The lymphatic system in the kidneys has a harmonious dynamic with ureteral and venous outflow, which can result in pathology when this dynamic is disturbed. Although limited by the small size of lymphatics, multiple established and emerging imaging techniques are available to visualize perinephric lymphatics. Manifestations of perirenal pathology may be in the form of dilation of perirenal lymphatics, as with peripelvic cysts and lymphangiectasia. Lymphatic collections may also occur, either congenital or as a sequela of renal surgery or transplantation. The perirenal lymphatics are also intimately involved in lymphoproliferative disorders, such as lymphoma as well as the malignant spread of disease. Although these pathologic entities often have overlapping imaging features, some have distinguishing characteristics that can suggest the diagnosis when paired with the clinical history.

The Pattern of Dyslipidemia in Chronic Liver Disease Patients.

Introduction Patients with chronic liver disease are expected to report derangements in serum lipid profiles. Lipid profile monitoring is not a part of the routine management of these patients in our hospital. Few recent studies show how lipid profile varies with the severity of disease and should be considered in the management planning of such patients. The objective of this study was to determine the pattern of dyslipidemia in chronic liver disease patients. Materials and methods A cross-sectional study was conducted involving 171 patients of all genders aged between 18 years and 60 years presenting with chronic liver disease with disease severity graded on Child-Pugh class as A, B, and C. Lipid profile was acquired in all these patients and was compared across various subgroups. Individual serum lipid parameters were graded as normal, high, or very high. Each patient was required to provide written informed consent. Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp. Armonk, NY) was used to analyze data statistically, taking a p-value of ≤0.05 as significant. Results The mean age of patients was 51.2±7.3 years. The male to female ratio came out to be 1.5:1, with 103 (60.2%) male and 68 (39.8%) female patients included in the study. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. The mean body mass index (BMI) of these patients was 25.9±2.4 kg/m2. Mean serum values among Child-Pugh A, Child-Pugh B, and Child-Pugh C of low-density lipoproteins (LDL) (113.15±14.08 vs. 95.58±14.25 vs. 53.46±5.90 mg/dl; p-value 0.001), high-density lipoproteins (HDL) (50.60±3.19 vs. 40.70±2.95 vs. 35.40±3.88 mg/dl; p-value 0.001), total cholesterol (174.20±17.33 vs. 164.00±17.82 vs. 128.64±24.73 mg/dl; p-value 0.001), and triglycerides (127.15±8.98 vs. 100.84±27.12 vs. 93.36±25.56 mg/dl; p-value 0.001) decreased significantly with increasing severity of disease. Nineteen (11.1%) patients had hyperlipidemia (serum values of two or more parameters above normal) while 152 (88.9%) patients had normal lipid profile. When stratified, no statistically significant difference was found in the frequency of hyperlipidemia across various subgroups based on the patient's gender, age, duration, and severity of the disease, BMI, or diabetic and hypertensive status. Conclusions A substantial proportion of patients with chronic liver disease had hyperlipidemia which varied with the severity of disease on Child-Pugh classification. Routine monitoring of the lipid profile of such patients is necessary for timely identification and management of dyslipidemia to improve the outcome of such patients. It also suggests an important role of lipid profile in the risk stratification and treatment of chronic liver disease patients and warrants further studies in this regard.

The Outcomes of Extracorporeal Shock Wave Lithotripsy for High-Density Renal Stone on Non-Contrast Computed Tomography.

Introduction Urinary lithiasis is usually managed by extracorporeal shock wave lithotripsy (ESWL). Patients are examined using non-contrast computed tomography (NCCT) in order to evaluate the feasibility of ESWL, according to where the stone is located and how big is its size. The objective of this study is to determine the outcomes of ESWL in patients having high-density renal stone, evaluated using NCCT. Materials and methods A descriptive case series study was conducted in the Department of Urology, Sindh Institute of Urology & Transplantation, Karachi for six months. Patients of either gender aged between 25-50 years, who presented with solitary renal and ureteric calculi of 0.5-2 cm in diameter and high-density renal stones [>750 hounsfield units (HU)] were enrolled. ESWL was performed and a satisfactory outcome was defined as complete stone clearance in less than or equal to three ESWL sessions. Statistical Package for Social Sciences (SPSS) (IBM Corp., Armonk, NY) was used to analyze frequencies and percentages of the number of ESWL sessions, complete renal stone clearances, and satisfactory outcomes at the end of 12 weeks. A p-value of <0.05 was considered significant. Results The mean age of the patient was reported to be 34.08 ± 9.53 years. 51.6% male preponderance was noticed. Renal and ureteric stones were found in 69.7% and 30.3% of patients, respectively. 21.3% of patients showed stone clearance after two ESWL sessions, 27% of patients after three ESWL sessions, and 51.6% of patients after four ESWL sessions. Stone clearance was found in 58.2% of patients and a satisfactory outcome was found in 42.6% of patients. Conclusions Our results signify a satisfactory outcome of extracorporeal shock wave lithotripsy for high-density renal stone on non-contrast computed tomography. Further studies on a larger scale are needed to validate these results.

Mean Changes in Estimated Glomerular Filtration Rate in Patients Undergoing Percutaneous Nephrolithotomy Having Renal Stone Disease.

Background Urinary stone disease is associated with renal impairment because of obstruction and infection. Comorbidities include hypertension, dyslipidemia, diabetes, and impaired renal function. Furthermore, as recurrences are common in urolithiasis, such patients undergo many treatments throughout their life. Percutaneous nephrolithotomy (PCNL) is an effective treatment for renal stones with a diameter greater than 2 cm. The primary objective of this study was to observe the mean changes in estimated glomerular filtration rate (GFR) in patients undergoing PCNL having renal stone disease. Methodology This cross-sectional study was conducted for six months between June and November 2020 at a tertiary care hospital in Karachi, Pakistan. All male and female patients aged between 15 and 70 years who were diagnosed with renal stones using X-ray of the kidney, ureter, and bladder or using ultrasound of the abdomen and planned for PCNL were selected. Patients with any duration of kidney stone disease were included. Statistical Package for Social Sciences version 20.0 (IBM Corp., Armonk, NY, USA) was used to statistically analyze the data. Results The mean age of the patients was 41.11 ± 14.30 (17-70) years. A total of 61 (38.1%) patients were female and 99 (61.9%) were male. Mean preoperative GFR was 91.22 ± 5.88 mL/min which decreased to 83.64 ± 5.70 mL/min at 48 hours post-PCNL. GFR significantly decreased after surgery (p = 0.0001). Conclusions During early postoperative days, GFR was decreased in patients undergoing PCNL. Factors that may impair renal function should be avoided during the first few days after undergoing PCNL. Further large-scale studies are needed to investigate these changes in GFR in post-PCNL patients.

Chromatographic Separation of the Novel Hypoglycemic Drug Mitiglinide in its Bulk Powder and Pharmaceutical Formulation: Forced Degradation and Validated Stability-Indicating HPTLC/Densitometry and HPLC/UV Methods.

BACKGROUND: Mitiglinide (MTG) is one of meglitinides group which are used for treatment of type two diabetes mellitus. OBJECTIVE: Mitiglinide (MTG) is a novel oral hypoglycemic drug. The present work adopts two stability-indicating chromatographic methods for determination of MTG after being exposed to forced degradation using 4 M methanolic HCl for 12 h. METHODS: The first method is HPTLC/densitometry using methanol:chloroform:acetic acid (5:2.5:0.3 by volume) as the eluting system and silica gel 60 GF254 as the stationary phase; the separated bands were then scanned at 220 nm. The second method is HPLC/UV in which acetonitrile:methanol:0.05 M potassium dihydrogen orthophosphate (pH 3.5) (40:25:35 by volume) was used as the mobile phase and a Zorbax SB-C8 (250 × 4.6 mm, 5 µm) column as a stationary phase, at a flow rate of 1 mL/min and UV detection at 220 nm. RESULTS: As a result of acid hydrolysis, two degradants were obtained. The first one was benzyl succinic acid to which this study was performed. The second one lacked configuration and was unreadable using UV spectrometry. Linearity was in the range of 8-48 µg/band MTG for HPTLC and 10-80 µg MTG for HPLC. LOD and LOQ values were 1.85 and 5.62 µg/band for the HPTLC method and 2.14 and 6.49 µg/mL for the HPLC method, respectively. The Recovery % was 100.03 ± 1.464 and 99.61 ± 1.44 using the HPTLC and HPLC methods, respectively. The relative standard deviations (RSD, %) for intra- and inter-day assays were 1.111 and 1.430 for the HPTLC method, respectively, and those for the HPLC method were 1.377 and 0.866, respectively. The RSD, %, for robustness testing was 1.162 (saturation time of mobile phase) and 1.592 (change in ratio of methanol content) for the HPTLC method and 1.377 (mobile phase composition), 1.713 (detector wavelength) and 1.770 (mobile phase flow rate) for the HPLC method. CONCLUSIONS: The adopted methods were successfully applied for the determination of MTG in its pure form, in presence of its acid degradant and in its tablet dosage form. HIGHLIGHTS: Statistical comparison between the results obtained from the developed methods and those obtained by the reported HPLC method showed no significance difference.

Separation and determination of clopidogrel and its impurities by capillary electrophoresis.

Clopidogrel bisulphate, an anti-platelet drug, has been separated from its impurities, namely impurity A, B and C by capillary zone electrophoresis (CZE) using uncoated fused-silica capillary (50.0 microm internal diameter, 31.2cm total length). Four factors affected the separation: buffer concentration, pH of the buffer, concentration of the chiral selector and the applied voltage. Optimization and robustness studies were performed with the aid of reduced central composite experimental design. The buffer used was triethylamine-phosphoric acid and the chosen chiral selector was sulphated beta-cyclodextrin (SCD). The best separation was achieved by using 10mM buffer, pH 2.3, containing 5% (mass/volume (m/v)) SCD. Reversed polarity mode was used with an applied voltage of -12kV and the capillary temperature was maintained at 20 degrees C. The method was validated for quantitative determination of the drug. It offered a limit of detection (LOD) of 0.13 microg/ml, a limit of quantitation (LOQ) of 0.4 microg/ml, and a linearity range of 0.4-300 microg/ml. Commercial bulk samples were analyzed using the developed method.

Simultaneous determination of phenylephrine hydrochloride, guaifenesin, and chlorpheniramine maleate in cough syrup by gradient liquid chromatography.

A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.

A New Platform for Profiling Degradation-Related Impurities Via Exploiting the Opportunities Offered by Ion-Selective Electrodes: Determination of Both Diatrizoate Sodium and Its Cytotoxic Degradation Product.

Although the ultimate goal of administering active pharmaceutical ingredients (APIs) is to save countless lives, the presence of impurities and/or degradation products in APIs or formulations may cause harmful physiological effects. Today, impurity profiling (i.e., the identity as well as the quantity of impurity in a pharmaceutical) is receiving critical attention from regulatory authorities. Despite the predominant use of spectroscopic and chromatographic methods over electrochemical methods for impurity profiling of APIs, this work investigates the opportunities offered by electroanalytical methods, particularly, ion-selective electrodes (ISEs), for profiling degradation-related impurities (DRIs) compared with conventional spectroscopic and chromatographic methods. For a meaningful comparison, diatrizoate sodium (DTA) was chosen as the anionic X-ray contrast agent based on its susceptibility to deacetylation into its cytotoxic and mutagenic degradation product, 3,5-diamino-2,4,6 triiodobenzoic acid (DTB). This cationic diamino compound can be also detected as an impurity in the final product because it is used as a synthetic precursor for the synthesis of DTA. In this study, four novel sensitive and selective sensors for the determination of both DTA and its cytotoxic degradation products are presented. Sensors I and II were developed for the determination of the anionic drug, DTA, and sensors III and IV were developed for the determination of the cationic cytotoxic impurity. The use of these novel sensors not only provides a stability-indicating method for the selective determination of DTA in the presence of its degradation product, but also permits DRI profiling. Moreover, a great advantage of these proposed ISE systems is their higher sensitivity for the quantification of DTB relative to other spectroscopic and chromatographic methods, so it can measure trace amounts of DTB impurities in DTA bulk powder and pharmaceutical formulation without a need for preliminary separation.

Validated stability-indicating methods for determination of cilostazol in the presence of its degradation products according to the ICH guidelines.

Sensitive and selective stability-indicating assay methods (SIAMs) are suggested for the determination of cilostazol (CIL) in the presence of its acid, alkaline and oxidative degradation products. Developing SIAMs is necessary to carry out any stability study. Stress testing of CIL was performed according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing showed that CIL underwent acid, alkaline and oxidative degradation; on the other hand, it showed stability towards photo- and thermal degradation. Two chromatographic SIAMs were developed, namely HPLC and HPTLC methods. The concentration range and the mean percentage recovery were 1.0-31.0 microg/ml and 99.96+/-0.46 and 0.6-14.0 microg/spot and 99.88+/-1.10 for HPLC and HPTLC methods, respectively. In addition, derivative spectrophotometric methods were developed in order to determine CIL in the presence of its acid degradation product; these were performed by using the third derivative spectra (3D) and the first derivative of the ratio spectra (1DD) methods. The linearity range and the mean percentage recovery were 2.0-34.0 microg/ml and 100.27+/-1.20 for the (3D) method, while they were 2.0-30.0 microg/ml and 99.94+/-1.18 for the (1DD) method. Also, two chemometric-assisted spectrophotometric methods, based on using partial least squares (PLS) and concentration residual augmented classical least squares method (CRACLS), for the determination of CIL were developed. Both methods were applied on zero order spectra of the mixtures of CIL and its acid degradation product, the mean percentage recovery was 100.03+/-1.09 and 99.91+/-1.27 for PLS and CRACLS, respectively. All methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied on bulk powder and pharmaceutical formulations.

Determination of tetraconazole and diniconazole fungicide residues in tomatoes and green beans by capillary gas chromatography.

A sensitive gas chromatographic method using an electron-capture detector (ECD) has been developed for the determination of tetraconazole and diniconazole fungicide residues in tomatoes and green beans. The developed method consists of extraction with methanol, partition with methylene chloride, and column chromatographic clean-up, followed by capillary gas chromatographic determination. The recoveries of both fungicides were greater than 90% for both plant samples. The limits of determination of the method were 0.001 ppm for both fungicides. The method was applied to determine residues and the rate of disappearance of tetraconazole and diniconazole from tomatoes and green beans [open field treatment, 50 cc of Domark 10% EC (emulsifiable concentrate), and 35 cc of Sumi-eight 5% EC; both for 100 l of water]. The fungicides incorporated into the plants decreased rapidly with a half-life around 3 days for diniconazole and from 4.5 to 6.5 days for tetraconazole. No residues could be detected in the plants during the period of study of 21 days after field application. Hence, the plants could be used safely after that period of time.