Development and Validation of Liquid Chromatographic Method for the Determination of the Related Substances of Rifampicin

A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.

Analysis of bacitracin and its related substances by liquid chromatography tandem mass spectrometry

A suitable liquid chromatography quadrupole time-of-flight mass spectrometric(LC–Q-TOF–MS) method was developed for separation and characterization of related substances in bacitracin test drug. The separation was performed on Li Chrospher RP-18 column using methanol as mobile phase A and 0.2% ammonium acetate buffer solution as mobile phase B in gradient elution. A total of 12 related substances were detected through high resolution mass spectrometric determination in a positive electrospray ionization mode. They were identified as co-existing active components and degradation products of bacitracin through the analysis and elucidation of both the protonated parents and the product ions of all the related substances and their fragmentation pathways were also proposed.

Validated gradient stability indicating HPLC method for determining Diltiazem Hydrochloride and related substances in bulk drug and novel tablet formulation

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.

Analysis of ganciclovir and its related substances using high performance liquid chromatography and liquid chromatography-mass spectrometry methods

Objective High performance liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC/MS)methods were developed for the determination of ganciclovir and its related substances.Methods A Hypersil ODS2 column(4.6 mm×250 mm,5 μm)was used with a mobile phase of 0.02 M potassium dihydrogen phosphate buffer(pH 6.0)-methanol(92∶8)at a flow rate of 1.0 mL/min,and UV detector set at 254 nm was used for monitoring the eluents.Results The method was simple,rapid,selective and capable of separating all related substances at trace level with a detection limit of 0.04 μg/mL.It has been validated with respect to accuracy,precision,linearity,and limits of detection and quantification.The linearity range was 10.2-153.0 μg/mL with r=0.9998.The percentage recoveries ranged from 96.7% to 101.6%,and RSD was 1.24%-1.96%(n=5).Conclusion The method was found to be suitable not only for monitoring the reactions during the process development but also for quality control of ganciclovir.For identification of related substances,LC/MS was used.The mainly related substances of ganciclovir active pharmaceutical ingredients(API)were determined as guanine,(1,3-dioxolan-4-yl)methyl acetate,and diacetyl guanine.

Psychiatric and substance use disorders co-morbidities and hepatitis C: Diagnostic and treatment implications

Chronic hepatitis C virus(HCV) viral infection is the most common blood-borne viral infection and approximately 2%-3% of the world's population or 170-200 million people are infected. In the United States as many as 3-5 million people may have HCV. Psychiatric and substance use disorders(SUDs) are common co-morbid conditions found in people with HCV and are factors in predisposing people to HCV infection. Also, these co-morbidities are reasons that clinicians exclude people from antiviral therapy in spite of evidence that people with HCV and co-morbid psychiatric and SUD can be safely and effectively treated. Furthermore, the neuropsychiatric side effects of interferon(IFN), until recently the mainstay of antiviral therapy, have necessitated an appreciation and assessment of psychiatric co-morbidities present in people with HCV. The availability of new medications and IFNfree antiviral therapy medication combinations will shorten the duration of treatment and exposure to IFN and thus decrease the risk of neuropsychiatric side effects. This will have the consequence of dramatically altering the clinical landscape of HCV care and will increase the number of eligible treatment candidates as treatment of people with HCV and co-morbid psychiatric and SUDs will become increasingly viable. While economically developed countries will rely on expensive IFN-free antiviral therapy, less developed countries will likely continue to use IFN-based therapies at least until such time as IFNfree antiviral medications become generic. The current manuscript discusses the efficacy and viability of treating HCV in people with psychiatric and SUDs comorbidities, the treatment of the neuropsychiatric side effects of IFN-based therapies and the impact of new medications and new treatment options for HCV that offer the promise of increasing the availability of antiviral therapy in this vulnerable population.

Glucomannan for abdominal pain-related functional gastrointestinal disorders in children:A randomized trial

AIM:To assess the efficacy of glucomannan(GNN) as the sole treatment for abdominal pain-related functional gastrointestinal disorders(FGIDs).METHODS:We conducted a double-blind,placebocontrolled,randomized trial.Patients were recruited among children referred to the Department of Paediatrics,Medical University of Warsaw.Included in the study were children aged 7-17 years with abdominal pain-related FGIDs classified according to the Rome Ⅲ diagnostic criteria.The children were randomly assigned to receive GNN,a polysaccharide of 1,4-D-glucose and D-mannose,a soluble fiber from the Japanese Konjac plant,at a dosage of 2.52 g/d(1 sachet of 1.26 g 2 times a day),or a comparable placebo(maltodextrin) at the same dosage.The content of each sachet was dissolved in approximately 125 mL of fluid and was consumed twice daily for 4 wk.RESULTS:Of the 89 eligible children,84(94%) completed the study."No pain" and "treatment success"(defined as no pain or a decrease ≥ 2/6 points on the FACES Pain Scale Revised) were similar in the GNN(n = 41) and placebo(n = 43) groups [no pain(12/41 vs 6/43,respectively;RR = 2.1,95%CI:0.87-5.07) as well as treatment success(23/41 vs 20/43;RR = 1.2,95%CI:0.79-1.83)].No significant differences between the groups were observed in the secondary outcomes,such as abdominal cramps,abdominal bloating/gassiness,episodes of nausea or vomiting,or a changed in stool consistency.GNN demonstrated no significant influence on the number of children requiring rescue therapy,school absenteeism,or daily activities.CONCLUSION:In our setting,GNN,as dosed in this study,was no more effective than the placebo in achieving therapeutic success in the management of FGIDs in children.

Analysis of fluoxetine-induced plasticity mechanisms as a strategy for understanding plasticity related neural disorders

Fluoxetine hydrochloride,better known for its commercial name Prozac,is one of the most widely prescribed antidepressant drugs all over the world.This drug was considered a＂breakthrough drug＂for the treatment of depression because of its very high selectivity as a serotonin reuptake inhibitor and because it presented a lower side-effectprofile than previous drugs （Wong et al., 2005）.

Identification and characterization of related substances in EVT-401 by hyphenated LC–MS techniques

A sensitive and selective method was developed for the separation and characterization of related substances(RSs) in EVT-401 by hyphenated LC–MS techniques. Complete separation of the RSs was achieved with an Inertsil ODS-SP column(250 mm×4.6 mm, 5 μm) by linear gradient elution using a mobile phase consisting of 0.2% formic acid solution, methanol and acetonitrile. EVT-401 was found to be susceptible to acid, alkaline and oxidative stresses, while relatively stable under photolytic and thermal dry stress conditions. Fourteen RSs including six process-related substances and eight degradation products were detected and identified in EVT-401 with positive ESI high-resolution TOF-MS analysis of their parent ions and the corresponding product mass spectra elucidation, and some of them were further verified by chemical synthesis and NMR spectroscopy. The specific LC–MS method developed for separation, identification and characterization of RSs is valuable for EVT-401 manufacturing process optimization and quality control.

Determination of 9-Deoxo-9a-Aza-9a-Homoerythromycin A and Related Substances by High-Performance Liquid Chromatography

A high-performance liquid chromatography（HPLC） method was developed and validated for the assay of 9-deoxo-9a-aza-9a-homoerythromycin A and related substances that might coexist in products as impurities that originate from the synthesis processes. A chromatographic system comprising an ODS 150 mm× 4.6 mm I.D. column, a mobile phase of cetonitrile monobasic potassium phosphate buffer （25/75）, a flow rate of 1.2 mL/min, a temperature of 30 ℃and a UV detector set at 205 nm has shown good chromatographic separation for 9-deoxo-9a-aza-9a-homoerythromycin A and other related substances. The linearity of the calibration curves, the precision, expressed as relative standard deviations, of the HPLC method have been studied. The HPLC method under study was found to be specific, precise, accurate and reproducible, indicating stability.

Validation of a Classification System for Obsessive-Compulsive and Related Disorders Based on DSM-5

The purpose of this study was to examine whether a broad?obsessive-compulsive and related disorders model, which consisted of obsessive-compulsive, hoarding disorder, body dysmorphic, trichotillomania and pathological skin picking, displayed sufficient data fit. On the other hand, we examined whether a reduced obsessive-compulsive and related disorders symptoms model consisting of above mentioned disorders demonstrated superior fit or not. To test the factor structure validity of the classification system of obsessive-compulsive spectrum disorders, we used Confirmatory Factor Analyses (CFA). Result of factor structure analysis revealed and supported an OCSD symptoms dimension that included obsessive-compulsive, hoarding disorder, body dysmorphic, trichotillomania, and pathological skin picking symptoms. Also, results of this study supported?the DSM-5 changes.

Brain reward circuitry:The overlapping neurobiology of trauma and substance use disorders

Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community samples.The possibility of a shared aetiology remains an important question in translational neuroscience.Advancements in genetics,basic science,and neuroimaging have led to an improved understanding of the neural basis of these disorders,their frequent comorbidity and high rates of relapse remain a clinical challenge.This project aimed to conduct a review of the field’s current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD.A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders,and is summarized in detail,including evidence from both animal and clinical studies.Upon summarizing the relevant literature,this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues.It provides an overview of brain reward circuitry and its relation to the neurobiology,symptomology,and phenomenology of trauma and substance use.This review provides clinical insights and implications of the proposed theory,including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology.Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.

Telehealth for Substance Use Disorders Treatment in Nigeria: Implementation Strategies Post-COVID-19

The COVID-19 pandemic has changed the way healthcare services are delivered. These changes will likely persist as countries recover from the economic crises following lockdowns. In developing countries, services for substance use disorders (SUDs) are inadequate and as countries prioritize infectious diseases, individuals with SUDs may suffer further neglect. This paper is a narrative review of peer-reviewed and grey literature on the current challenges with SUD treatment in Nigeria assesses how telehealth may positively affect access to evidence-based treatments and suggests strategies for implementation considering the unique challenges and opportunities in the country. If prioritized in her policy, telehealth has the potential to improve treatment outcomes for SUDs in Nigeria.

Cefotiam hydrochloride for injection of related substance in clavulante potassium by LCMS-IT-TOF

Objective: To analyze the related substances in Cefotiam Hydrochloride for Injection. Methods: HPLC-IT-TOF, the HPLC condition: C18 (250 mm×4.6 mm, 5 μm);temp: 30℃;mobile phase: A) 0.02 mol/L ammonium acetic;B) methanol;flow tate: 1.0 mL/min;postcoiumn split ratio: 1:1;detection: UV254;elute by linear gradient. MS parameter: ion source: ESI(+);100-1000 m/z;ionization voltage: 3.0 kV;dry gas (N2);temp: 200 ℃;emale cone voltage 30 V(1)Result: Eight related substances were separated in products, of which three were elucidated in the production, Others are degradation impurities. Conclusion: There were several related substances during production of Cefotiam.LCMS-IT-TOF provided an effective method to determine the related substances and ensure the quality and safety of the product.

LC-MS/MS Method Applied to the Detection and Quantification of Ursodeoxycholic Acid Related Substances in Raw Material and Pharmaceutical Formulation

Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.

ⅩⅩ World Congress on Parkinson's Disease and Related Disorders

Time:December 8-11,2013Venue:Palexpo Geneva Congress Center,Geneva,Switzerland Email:Parkinson@kenes.com Website:www2.kenes.com/parkinson/Pages/Home.aspxⅩⅩ World Congress on Parkinson’s Disease and Related Disorders will be held on December 8-11,2013 in Geneva,Switzerland.As the motto for this World Congress is'Integration by Translation',this Congress will deal in a most translational way with most recent research and updates on the etiology,pathogenesis,potential diagnostic markers and treatment modalities

Introduction of The Chinese Journal of Alzheimer's Disease & Related Disorders

The Chinese Journal of Alzheimer’s Disease&Related Disorders, the first journal dedicated to Alzheimer’s disease and related neurodegenerative diseases in China, was founded by Chinese Association for Alzheimer’s disease (CAAD)(CN 10-1536/R, ISSN 2096—5516) in early 2018.

Epidemiological Patterns of Work-Related Musculoskeletal Disorders among Healthcare Workers in Five Reference Hospitals in the City of Douala, Cameroon

Introduction: Work-related musculoskeletal disorders (WRMSDs) are a public health problem and have forced many workers to quit their jobs prematurely. This study investigated the prevalence and risk factors of WRMSDs among Healthcare workers in five reference hospitals in the City of Douala-Cameroon. Methods: A cross-sectional study was conducted in 2022 among 561 healthcare workers working in five reference hospitals in the city of Douala, Cameroon. Participants were selected using a convenient sampling technique. Data were collected with structured questionnaires;data on the demographics and risk factors were collected using a well-designed questionnaire, while estimation of the prevalence of WRMSDs was done using the Modified Nordic questionnaire. Results: The overall prevalence rate of WRMSDs among healthcare workers in Douala hospitals was 83.4% (468/561). The prevalence per professional groups was as follows: 88.8% (71) for Medical Laboratory Scientists (MLS), 81.9% (289) for nurses, 21 (80.8%) for Physiotherapists (PTs) and 78.8% (41) for Medical Doctors (MDs). There was a significant difference (p = 0.001) in the prevalence of WRMSDs with respect to place of work where healthcare workers from HLD recorded the highest prevalence 89.9%, while Healthcare workers from NBDH were 2.91 times at risk (AOR = 2.91;95% CI: 1.32 - 6.41;p = 0.001) to develop WRMSDs than healthcare workers in the other hospitals. With respect to body region, the highest prevalence of WRMSDs was recorded on the lower back, 58.8% with the lowest at the elbows 11.2%. The age group 30 to 39 years was significantly associated with WRMSDs at level of the shoulder (p = 0.002), upper back (p = 0.019), elbows (p Conclusion: The overall prevalence rate of WRMSDs among healthcare workers in Douala hospitals was high. The prevalence of WRMSDs is highest among MLS and nurses and the most affected body parts are;lower back, neck and upper back. Working on the same posture, stressful job, and repetitive tasks were the major risk factors associated to WRMSDs among healthcare workers in Douala hospitals.

Therapeutic Effects of an Alpha-Casozepine and White Fish Muscle Hydrolyzed Complementary Feed on Canine Separation-Related Disorders and Quality of Life of Dogs and Their Pet Owners

Background: Separation-related disorders are prevalent in dogs and can result in problem behaviours such as inappropriate elimination, destructive behaviour, and distress vocalizations which occur when an owner is absent or perceived as absent. Numerous natural products are marketed for managing anxiety in dogs;however, few, if any, of these products have documented evidence of efficacy in veterinary behaviour. Purpose: This open, multicentric clinical trial aimed to assess the efficacy of a new supplement containing alpha-casozepine and fish muscle hydrolysate on the separation-related problem in dogs and the impact on the quality of life of dogs and their pet owners. Material and Methods: Fifty-one dogs with clinical signs compatible with separation-related problems were included. The dogs were treated with a complementary feed (Zylkene Plus, Vetoquinol, France) for 30 days. Separation-related behaviour assessment (SRP), emotional disorders assessment (EDED) and the quality of life (QoL) of the pets and their pet owner were assessed at baseline and the end of the study by the veterinarians. In addition, owners were asked to rate their dog’s SRP weekly after enrolment using the same questionnaire that the veterinarian used at the beginning of the study. Results: There was a statistically significant improvement in the SRP, EDED, and QoL scores (P Conclusion: The results of this study support the hypothesis that the combination of alpha-casozepine and fish muscle hydrolysate is a promising and effective option to reduce the frequency and severity of separation-related behaviour in dogs and improve the quality of dogs and their owners.

Influence of Metabolic Syndrome versus Musculoskeletal Disorders on Saudi Health-Related Quality of Life

Aim: This work aimed to study the influence of two chronic health conditions, metabolic syndrome (MetS) and musculoskeletal disorders (MSDs), on the health-related quality of life (HRQoL) of Saudis. Method: The Medical Outcomes Study Short Form-36 (SF-36) health status questionnaire was used to measure the HRQoL and compare the mean scores of the questionnaire subscales and physical and mental component summaries (PCS and MCS) of 33 patients with MetS, 18 patients with MSDs, and 30 apparently healthy (AH) subjects. Regression analysis was used to measure the prediction power of the study group, age and gender of the participants in estimating the HRQoL. Results: Results showed that the mean scores of the physical subscales, the PCS, the mental subscales and MCS were arranged in descending order from AH subjects, patients with MetS, to patients with MSDs. The mean scores difference among the 3 study groups were statistically significant with the only exception for the general mental health (GMH) subscale (P = 0.404). The study group and age accounted for 41.8% of the variability of PCS while the study group accounted for 19.6% of the variability in the MCS. The resulted equation to estimate the PCS score was as follows: PCS = 113.18 - 12.85 (Group: 0 for AH, 1 for MetS, and 2 for MSDs) - 0.67 age. On the other hand the resulted equation to estimate the MCS score was as follows: MCS = 76.203 - 10.426 (Group: 0 for AH, 1 for MetS, and 2 for MSDs). Conclusion: Patients with MetS and patients with MSDs had lower HRQoL than AH subjects. All the physical and mental dimensions of HRQoL are negatively influenced with MetS and with MSDs with the only exception for the GMH subscale. The physical and mental burden of MSDs is more dominant. The study group and age can be used to predict the PCS while the study group can be used to predict the MCS.

Vertebro-basilar ischemic attacks and sleep-related breathing disorders

Objective To study the relationship between vertebro basilar ischemic attacks (VBI) and sleep related breathing disorders (SRBD). Methods Polysomnographic examinations were performed on 45 VBI patients. The incidence and characteristics of SRBD, and its relationship with various clinical factors were analyzed. Results Eighteen cases (40%) were complicated with SRBD, among which 2/3 was obstructive and 1/3 was central types. They were correlated with obesity and prone to be suffered with cardiovascular disorders.Conclusions Brain stem dysfunction caused by long term repeated ischemias probably is the pathogenesis of SRBD, especially it’s central type, in VBI. The arrhythmia and hypertension secondary to SRBD may aggravate VBI. VBI and SRBD may be reciprocal and form a vicious circle which should draw attention in the prevention and treatment of SRBD in VBI.