المؤلفون: Sinha, Shubhadeep D.¹ (AUTHOR), Perapogu, Sridevi² (AUTHOR), Chary S., Sreenivasa¹ (AUTHOR), Ramesh, S.³ (AUTHOR), Bakshi, Jaimanti⁴ (AUTHOR), Singh, Ajit⁵ (AUTHOR), Ahmed, Abdul Khabeer⁶ (AUTHOR), Mohan Reddy, B.¹ (AUTHOR), Panapakam, Muralidhar¹ (AUTHOR), Talluri, Leela¹ (AUTHOR) leela.t@hetero.com, Vattipalli, Ramya¹ (AUTHOR)

المصدر: Journal of Asthma. Nov2023, Vol. 60 Issue 11, p2014-2020. 7p.

مصطلحات موضوعية: *ALLERGIC rhinitis, *LEUKOTRIENE antagonists, *INFLAMMATORY mediators, *ADULTS, *PATIENT safety, *SUBLINGUAL immunotherapy, *ALLERGIC conjunctivitis

مصطلحات جغرافية: INDIA

مستخلص: Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR. [ABSTRACT FROM AUTHOR]

المؤلفون: Fawbert, Katherine, Leech, Susan

المصدر: Paediatrics & Child Health; Jun2024, Vol. 34 Issue 6, p179-185, 7p

مصطلحات موضوعية: CHRONIC disease diagnosis, THERAPEUTIC use of monoclonal antibodies, LEUKOTRIENE antagonists, STEROIDS, ORAL drug administration, CHRONIC diseases, ANTIHISTAMINES, AUTOIMMUNE diseases, URTICARIA, ANGIONEUROTIC edema, TRANEXAMIC acid, CHILDREN

مستخلص: Urticaria commonly occurs in childhood, affecting up to 15% of British children. It is characterized by the sudden onset of wheals, angioedema, or both. Episodes are usually acute, often triggered by viral infections or antibiotics, with approximately a third progressing to chronic or recurrent urticaria. This review focuses on chronic urticaria subtypes, diagnosis and treatment options for children. The diagnosis is usually made clinically, and a focused history is key. Detailed investigation is usually unnecessary. Chronic urticaria is divided into chronic spontaneous urticaria and the inducible urticarias. Chronic spontaneous urticaria is autoimmune in origin, in approximately 40% of older children. Cold urticaria and dermographism are the most common inducible urticarias. Isolated angioedema should prompt consideration of hereditary angioedema. The mainstay of treatment is trigger avoidance combined with non-sedating antihistamines. Higher doses of antihistamines may be required but these are usually tolerated well. We provide guidance on antihistamine updosing strategies. There is an improvement in symptoms for most children, but leukotriene receptor antagonists can provide additional improvements in some children. Tranexamic acid may provide symptomatic relief for isolated angioedema. Short courses of oral steroids may be used in acute episodes or highly symptomatic patients with chronic urticaria. Second line treatment for non-responders is primarily monoclonal anti-IgE antibody therapy but a small number of children and young people continue to have significant symptoms despite this and in these children ciclosporin may be useful. Urticaria usually resolves and almost all children and young people are disease free after 7 years. [ABSTRACT FROM AUTHOR]

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المؤلفون: Manuel, Astrid M, Gottlieb, Assaf, Freeman, Leorah, Zhao, Zhongming

المصدر: Multiple Sclerosis Journal; May2024, Vol. 30 Issue 6, p696-706, 11p

مصطلحات موضوعية: DRUG additives, MONTELUKAST, MULTIPLE sclerosis, CLINICAL trials, LEUKOTRIENE antagonists

مستخلص: Background: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. Objective: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). Methods: In this retrospective case–control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18–65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics^® Data Mart (CDM) and IQVIA PharMetrics^® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. Results: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. Conclusion: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs' potential mechanism in MS. [ABSTRACT FROM AUTHOR]

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المؤلفون: Yutaro Imaichi, Eiji Nakatani, Yuma Fukutomi, Nagato Kuriyama, Kiyoshi Mori, Akira Sugawara

المصدر: Epilepsia Open, Vol 9, Iss 1, Pp 200-209 (2024)

مصطلحات موضوعية: allergic rhinitis, asthma, epilepsy, leukotriene antagonists, seizures, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Objective Managing the risk of epileptic seizures in older adults is increasingly important as the population ages. Leukotriene receptor antagonists (LTRAs) are commonly used to treat asthma or allergic rhinitis. Preclinical studies suggest that LTRAs have antiepileptic effects; however, few population‐based etiological studies on this topic have been available. Our study explored whether LTRAs reduce hospitalization risk associated with epileptic seizures in older individuals with asthma or allergic rhinitis. Methods We conducted a new‐user design analysis using the Shizuoka Kokuho database. We included all individuals aged 60‐89 years who had at least one episode of allergic rhinitis or asthma during the study period. We compared individuals who newly started LTRAs with those who did not take LTRAs. Propensity score matching was used to balance the baseline characteristics of the participants. We compared the hazard ratios for seizure‐related hospitalization between new LTRA users and non‐users and performed subgroup analyses. Results Our matched cohorts consisted of 64 724 new users and non‐users of LTRAs who were aged 60‐89 years and had asthma or allergic rhinitis. During the observation period, 377 (0.58%) and 595 (0.92%) incidents were observed in the LTRA new‐user and non‐user groups, respectively. The hazard ratio for seizure‐related hospitalization was 0.75 (95% confidence interval [CI]: 0.62‐0.92) in the LTRA new‐user group compared with the non‐user group. Subgroup analysis revealed that the hazard ratio was weak in diabetic patients (1.31; 95% CI: 0.72‐2.38). Significance This study indicated that LTRAs reduced seizure‐related hospitalization in older adult patients with allergic rhinitis or asthma. We could not evaluate the severity and related diseases of epileptic seizures during LTRAs. Further studies, including observational studies, detailed multicenter prospective studies, and clinical trials, are needed to validate these findings. Plain Language Summary This study examined if leukotriene receptor antagonists (LTRAs), commonly used for asthma or allergies, could lower seizure risk in older adults. Analyzing health records of 60‐89 year‐olds with asthma or allergies, we found a reduced rate of seizure‐related hospitalizations in those starting LTRAs, though this was not as evident in diabetic patients. Our results suggest potential benefits of LTRAs in preventing seizures in older adults with respiratory issues, but further research is needed to confirm these findings.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2470-9239Test

الوصول الحر: https://doaj.org/article/50397e84f1be48c98e8067b5d02439c4Test

المؤلفون: Kaya‐Yasar, Yesim, Engin, Seckin, Barut, Elif Nur, Inan, Cihan, Saygin, Ismail, Erkoseoglu, Ilknur, Sezen, Sena F.

المصدر: Drug Development Research; Apr2024, Vol. 85 Issue 2, p1-13, 13p

مصطلحات موضوعية: OVALBUMINS, LIPOPOLYSACCHARIDES, MONTELUKAST, LEUKOTRIENE antagonists, INFLAMMATION, KOUNIS syndrome, GENE expression

مستخلص: The wingless/integrase‐1 (WNT) pathway involved in the pathogenesis of inflammatory airway diseases has recently generated considerable research interest. Montelukast, a leukotriene receptor antagonist, provides therapeutic benefits in allergic asthma involving eosinophils. We aimed to investigate the role of the WNT pathway in the therapeutic actions of montelukast (MT) in a mixed type of allergic‐acute airway inflammation model induced by ovalbumin (OVA) and lipopolysaccharide (LPS) in mice. Female mice were sensitized with intraperitoneal OVA‐Al(OH)3 administration in the initiation phase and intranasal OVA followed by LPS administration in the challenge phase. The mice were divided into eight groups: control, asthmatic, and control/asthmatic treated with XAV939 (inhibitor of the canonical WNT pathway), LGK‐974 (inhibitor of the secretion of WNT ligands), or MT at different doses. The inhibition of the WNT pathway prevented tracheal 5‐HT and bradykinin hyperreactivity, while only the inhibition of the canonical WNT pathway partially reduced 5‐HT and bradykinin contractions compared to the inflammation group. Therefore, MT treatment hindered 5‐HT and bradykinin hyperreactivity associated with airway inflammation. Furthermore, MT prevented the increases in the phosphorylated GSK‐3β and WNT5A levels, which had been induced by airway inflammation, in a dose‐dependent manner. Conversely, the MT application caused a further increase in the fibronectin levels, while there was no significant alteration in the phosphorylation of the Smad‐2 levels in the isolated lungs of the mice. The MT treatment reversed the increase in the mRNA expression levels of interleukin‐17A. An increase in eosinophil and neutrophil counts was observed in bronchoalveolar lavage fluid samples obtained from the mice in the inflammation group, which was hampered by the MT treatment. The inhibition of the WNT pathway did not alter inflammatory cytokine expression or cell infiltration. The WNT pathway mediated the therapeutic effects of MT due to the inhibition of GSK‐3β phosphorylation as well as the reduction of WNT5A levels in a murine airway inflammation model. [ABSTRACT FROM AUTHOR]

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المؤلفون: Kordjazy, Nastaran, Amini, Shahideh

المصدر: Therapeutic Advances in Respiratory Disease; 3/19/2024, p1-12, 12p

مصطلحات موضوعية: BRONCHIOLITIS obliterans syndrome, LEUKOTRIENE antagonists, CELL transplantation, HEMATOPOIETIC stem cell transplantation, BONE marrow transplantation

مستخلص: Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft- versus -host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed. Plain language summary: A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantation Lung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed. [ABSTRACT FROM AUTHOR]

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المؤلفون: Ora, Josuel, De Marco, Patrizia, Gabriele, Mariachiara, Cazzola, Mario, Rogliani, Paola

المصدر: Journal of Functional Morphology & Kinesiology; Mar2024, Vol. 9 Issue 1, p15, 13p

مصطلحات موضوعية: EXERCISE-induced asthma, METERED-dose inhalers, PULMONARY function tests, ADRENERGIC beta agonists, INHALERS, LEUKOTRIENE antagonists, ELITE athletes, WATER chlorination

الشركة/الكيان: EUROPEAN Investment Bank

مستخلص: Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among athletes, particularly those competing at elite levels, the prevalence of respiratory conditions is notably heightened, varying between 20% and 70% across specific sports. Exercise-induced bronchoconstriction (EIB) is a common issue among athletes, impacting their performance and well-being. The prevalence rates vary based on the sport, training environment, and genetics. Exercise is a known trigger for asthma, but paradoxically, it can also improve pulmonary function and alleviate EIB severity. However, athletes' asthma phenotypes differ, leading to varied responses to medications and challenges in management. The unique aspects in athletes include heightened airway sensitivity, allergen, pollutant exposure, and temperature variations. This review addresses EIB in athletes, focusing on pathogenesis, diagnosis, and treatment. The pathogenesis of EIB involves complex interactions between physiological and environmental factors. Airway dehydration and cooling are key mechanisms, leading to osmotic and thermal theories. Airway inflammation and hyper-responsiveness are common factors. Elite athletes often exhibit distinct inflammatory responses and heightened airway sensitivity, influenced by sport type, training, and environment. Swimming and certain sports pose higher EIB risks, with chlorine exposure in pools being a notable factor. Immune responses, lung function changes, and individual variations contribute to EIB in athletes. Diagnosing EIB in athletes requires objective testing, as baseline lung function tests can yield normal results. Both EIB with asthma (EIBA) and without asthma (EIBwA) must be considered. Exercise and indirect bronchoprovocation tests provide reliable diagnoses. In athletes, exercise tests offer effectiveness in diagnosing EIB. Spirometry and bronchodilation tests are standard approaches, but the diagnostic emphasis is shifting toward provocation tests. Despite its challenges, achieving an optimal diagnosis of EIA constitutes the cornerstone for effective management, leading to improved performance, reduced risk of complications, and enhanced quality of life. The management of EIB in athletes aligns with the general principles for symptom control, prevention, and reducing complications. Non-pharmacological approaches, including trigger avoidance and warming up, are essential. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy in athletes. Short-acting beta agonists (SABA) are discouraged as sole treatments. Leukotriene receptor antagonists (LTRA) and mast cell stabilizing agents (MCSA) are potential options. Optimal management improves the athletes' quality of life and allows them to pursue competitive sports effectively. [ABSTRACT FROM AUTHOR]

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المؤلفون: Imaichi, Yutaro, Nakatani, Eiji, Fukutomi, Yuma, Kuriyama, Nagato, Mori, Kiyoshi, Sugawara, Akira

المصدر: Epilepsia Open; Feb2024, Vol. 9 Issue 1, p200-209, 10p

مصطلحات موضوعية: LEUKOTRIENE antagonists, ALLERGIC rhinitis, OLDER people, DATABASES, METERED-dose inhalers, OLDER patients, COHORT analysis, INHALERS

مستخلص: Objective: Managing the risk of epileptic seizures in older adults is increasingly important as the population ages. Leukotriene receptor antagonists (LTRAs) are commonly used to treat asthma or allergic rhinitis. Preclinical studies suggest that LTRAs have antiepileptic effects; however, few population‐based etiological studies on this topic have been available. Our study explored whether LTRAs reduce hospitalization risk associated with epileptic seizures in older individuals with asthma or allergic rhinitis. Methods: We conducted a new‐user design analysis using the Shizuoka Kokuho database. We included all individuals aged 60‐89 years who had at least one episode of allergic rhinitis or asthma during the study period. We compared individuals who newly started LTRAs with those who did not take LTRAs. Propensity score matching was used to balance the baseline characteristics of the participants. We compared the hazard ratios for seizure‐related hospitalization between new LTRA users and non‐users and performed subgroup analyses. Results: Our matched cohorts consisted of 64 724 new users and non‐users of LTRAs who were aged 60‐89 years and had asthma or allergic rhinitis. During the observation period, 377 (0.58%) and 595 (0.92%) incidents were observed in the LTRA new‐user and non‐user groups, respectively. The hazard ratio for seizure‐related hospitalization was 0.75 (95% confidence interval [CI]: 0.62‐0.92) in the LTRA new‐user group compared with the non‐user group. Subgroup analysis revealed that the hazard ratio was weak in diabetic patients (1.31; 95% CI: 0.72‐2.38). Significance: This study indicated that LTRAs reduced seizure‐related hospitalization in older adult patients with allergic rhinitis or asthma. We could not evaluate the severity and related diseases of epileptic seizures during LTRAs. Further studies, including observational studies, detailed multicenter prospective studies, and clinical trials, are needed to validate these findings. Plain Language Summary: This study examined if leukotriene receptor antagonists (LTRAs), commonly used for asthma or allergies, could lower seizure risk in older adults. Analyzing health records of 60‐89 year‐olds with asthma or allergies, we found a reduced rate of seizure‐related hospitalizations in those starting LTRAs, though this was not as evident in diabetic patients. Our results suggest potential benefits of LTRAs in preventing seizures in older adults with respiratory issues, but further research is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

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المؤلفون: Miida, Hiroshi¹ (AUTHOR) hiromii@cameo.plala.or.jp

المصدر: International Journal of Dermatology. Apr2023, Vol. 62 Issue 4, pe267-e270. 4p.

مصطلحات موضوعية: *URTICARIA, *LEUKOTRIENE antagonists, *TREATMENT effectiveness

مستخلص: UCT scores increased significantly after treatment with both H2A and LA in combination with second-generation H1-antihistamines than UCT scores before the treatment (P = 0.001). In conclusion, treatment with both LA and H2A in combination with sgH1AH is worth being applied for CIU refractory to sgH1AH alone before using oral corticosteroids or more expensive medications. In the EAACI/GA SP 2 sp LEN/EuroGuiDerm/APAAACI guideline,[1] treatment with two kinds of sgH1AH, H2-antagonists (H2A) or leukotriene antagonists (LA) are not recommended in the algorithm because of low-quality evidence. [Extracted from the article]

المؤلفون: Vadagam, Niroja, Haridasyam, Sharath Babu, Venkatanarayana, Muvvala, Lakka, Narasimha S., Chinnakadoori, Sanjeeva R.

المصدر: Chirality; Dec2023, Vol. 35 Issue 12, p952-965, 14p

مصطلحات موضوعية: DRUGS, DRUG tablets, HIGH performance liquid chromatography, MONTELUKAST, ENANTIOMERS, LEUKOTRIENE antagonists

الشركة/الكيان: UNITED States Pharmacopeial Convention

مستخلص: Montelukast sodium (MLS) is a leukotriene receptor antagonist that relieves asthma, bronchospasm, allergic rhinitis, and urticaria. A simple, robust, and stability‐indicating normal phase high‐performance liquid chromatography method was developed to separate and quantitatively estimate the S‐enantiomer of MLS. The chiral separation was achieved using USP L51 packing material along with a mobile phase consisting of a solvent mixture (n‐hexane, ethanol, and propionic acid), a flow rate of 1.0 mL/min, a detection wavelength of 284 nm, a column temperature of 30°C and an injection volume of 20 μL. The enantiomers peaks were well separated from the peaks of the placebo, diluting solvent, MLS, and its known impurities with a resolution of more than 2.2 and with no interference. Accuracy and linearity were studied in a range of 0.36–3.597 μg/mL (0.03%–0.30%), with good recoveries between 92.5% and 96.8% and a linear regression coefficient above 0.996. The suggested chiral chromatography method is being considered as an alternative and equivalent method to the United States Pharmacopeia and European Pharmacopeia monographs. The developed method was effectively employed for the study of release and stability samples of MLS. This HPLC method is also capable of separating and estimating the stereo‐selective isomers (R‐ and S‐enantiomers) of sulfoxide impurity of MLS in pharmaceutical medicine. [ABSTRACT FROM AUTHOR]

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