Tiopronin 250mg tablets

Neural epidermal growth factor-like 1 protein (NELL-1) was first identified as a membranous antigen by Sethi et al.1 utilizing laser capture microdissection and mass spectrometry followed by immunostaining. NELL-1 is currently the most common non-phospholipaseA2 receptor (PLA2R) membranous antigen. Segmental membranous changes are well-described in NELL-1 membranous nephropathy (MN).2 NELL-1 MN has been linked to malignancy, use of traditional indigenous medicines, and lipoic acid (LA) supplementation, among other conditions.

Abstract licence: CC BY-NC-ND

This study presents the development and validation of a novel reverse-phase ultra-high-performance liquid chromatography (UHPLC) method for quantifying tiopronin residues on manufacturing equipment surfaces as part of cleaning validation. Tiopronin, a synthetic thiol compound with therapeutic applications, requires stringent manufacturing controls to ensure product safety and efficacy. Existing analytical techniques mainly focus on quantifying tiopronin in pharmaceutical formulations or biological matrices. However, no methods specifically address cleaning validation for tiopronin production equipment. Using an Analytical Quality by Design approach, this UHPLC method was optimized and validated by ICH Q2 (R2) guidelines. The technique employs a Waters ACQUITY UPLC H-Class PLUS C-18 column (100 mm × 2.1 mm, 1.7 µm) with a mobile phase of 88:12 (v/v) 0.1% v/v orthophosphoric acid (pH 2.1) and acetonitrile, achieving a tiopronin retention time of 1.3 min. The method demonstrated specificity, precision, accuracy, and linearity over a concentration range of 0.302 to 3.027 µg/mL. The limit of detection and quantification were 0.100 µg/mL and 0.301 µg/mL, respectively. The greenness of the method was assessed using AGREE, GAPI, and RGB 12 tools. The scores obtained were 0.67 for AGREE, 85.0 for BAGI, and 82.1 for RGB 12 suggesting proposed method is environment friendly. This novel method provides an efficient, eco-friendly solution for routine cleaning validation, addressing a significant gap in existing analytical techniques for tiopronin manufacturing.

Abstract licence: CC BY-NC-ND

Cystinuria, characterized by defective renal absorption of cystine causing recurrent nephrolithiasis, demands ongoing management. This study examines the effects of COVID-19-related disruptions in tiopronin availability on the clinical outcomes of pediatric cystinuria patients. This retrospective cohort study analyzed medical records of 11 pediatric patients with cystinuria, followed from 2001 to 2023. Patients were diagnosed using urine microscopy/biochemistry and stone composition analysis. Clinical outcomes, including renal function and stone status, were assessed using serial ultrasonographic evaluations and 24-hour urinary cystine measurements. At diagnosis, the median age was 13 months, and 63.6% were female. Acute kidney injury was observed in 36.4% of patients, with 27.3% requiring emergency dialysis. The interruption of tiopronin treatment led to significant renal function deterioration and increased stone burden, as evidenced by an increase in the median number of kidney stones from 2 (IQR: 1-3) to 4 (IQR: 2-5, p = 0.045) and a rise in 24-hour urinary cystine levels from 286 mg/1.73 m² (IQR: 82-552.5) to 434 mg/1.73 m² (IQR: 198-854, p = 0.043). Data prior to the interruption showed a median glomerular filtration rate (GFR) of 80.4 mL/min/1.73 m² and creatinine levels of 2.47 mg/dL. After resuming tiopronin, there was a notable improvement to a median GFR of 161 mL/min/1.73 m² and creatinine levels of 0.48 mg/dL. Managing cystinuria during the pandemic underscored the critical role of continuous access to medications like tiopronin in preventing renal deterioration. Developing strategies to ensure an uninterrupted drug supply during global health emergencies is crucial for managing chronic conditions such as cystinuria.

Abstract licence: CC BY

Cystinuria is an inherited autosomal recessive disease of the kidneys of recurring nature that contributes to frequent urinary tract infections due to bacterial growth and biofilm formation surrounding the stone microenvironment. In the past, commonly used strategies for managing cystinuria involved the use of (a) cystine crystal growth inhibitors such as l-cystine dimethyl ester and lipoic acid, and (b) thiol-based small molecules such as N-(2-mercaptopropionyl) glycine, commonly known as tiopronin, that reduce the formation of cystine crystals by reacting with excess cystine and generating more soluble disulfide compounds. However, there is a dearth of simplistic chemical approaches that have focused on the dual treatment of cystinuria and the associated microbial infections. This work strategically exploited a single chemical approach to develop a nitric oxide (NO)-releasing therapeutic compound, S-nitroso-2-mercaptopropionyl glycine (tiopronin-NO), for the dual management of cystine stone formation and the related bacterial infections. The results successfully demonstrated that (a) the antibacterial activity of NO rendered tiopronin-NO effective against the stone microenvironment inhabitants, Escherichia coli and Pseudomonas aeruginosa, and (b) tiopronin-NO retained the ability to undergo disulfide exchange with cystine while being reported to be safe against canine kidney and mouse fibroblast cells. Thus, the synthesis of such a facile molecule aimed at the dual management of cystinuria and related infections is unprecedented in the literature.

Abstract licence: CC BY