Contact in context最新文献

{"title":"Spectral Intra-Lot and Inter-Lot Variability in Methacholine.","authors":"Uiyeol Yoon, Ayumi Tarianto, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Bailey Hall, Kyra Sharp, Madison Geib, Abby Wingate, Alexander Bacanurschi, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.31413281","DOIUrl":"10.6084/m9.figshare.31413281","url":null,"abstract":"<p><p>Methacholine chloride is a parasympathomimetic (cholinergic) bronchoconstrictor agent. It is administered exclusively in solution via inhalation for diagnostic purposes, strictly indicated for diagnosing bronchial airway hyperreactivity in adults and pediatric patients aged five years and older who lack clinically apparent asthma. Spectrometric evaluation of a single manufacturing batch, lot P3055R, revealed distinct anomalies, most notably a broad absorbance peak at 5131 cm^- ¹ that was present in certain vials but entirely absent in others. Principal component analysis orthogonally quantified this intralot variance, demonstrating that Vial 1 deviated by 7.3 standard deviations (SDs) from the cluster center, while a subsequent rotation identified Vial 4 as an outlier positioned 4.3 SDs away. Expanding the evaluation to a 39-vial library across three distinct lots (P3055R, P3048R, and P4009S) demonstrated significant interlot structural variance. This complexity required nine full principal components to model 99.97% of the cumulative variation. Furthermore, the application of the nonparametric FSOB (Fast Son of BEST) subcluster analysis algorithm inside the spectral clusters confirmed the geometric separation of the data into statistically significant sub-groups. Specifically, vials 8 through 18 naturally separated from the remaining library (vials 1 through 7 and 19 through 39). This geometric separation spanned an extensive correlation distance of 58.8 SDs, defined by the statistical metrics r_tn=0.9944, r_ts=0.8903, and <i>σ</i>=0.0019, with probability-density perturbations achieving a significance level of <i>p</i>=0.02. While these quantified deviations do not definitively prove the presence of adulteration or an excess level of impurities, they strongly indicate that the manufacturer's production pipeline may have drifted outside of a state of strict process control, warranting further investigation.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2026 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring Aztreonam Variations by Process Analytical Technology.","authors":"Uiyeol Yoon, Ayumi Tarianto, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Bailey Hall, Kyra Sharp, Madison Geib, Abby Wingate, Alexander Bacanurschi, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.32030886","DOIUrl":"10.6084/m9.figshare.32030886","url":null,"abstract":"<p><p>Aztreonam for injection (Fresenius Kabi) is a sterile, nonpyrogenic, sodium-free lyophilized, off-white to slightly yellow solid containing approximately 780 mg of arginine per gram of aztreonam, indicated for the treatment of specific infections caused by susceptible Gram-negative microorganisms. Ensuring the physical and chemical homogeneity of this lyophilized matrix is critical for consistent clinical efficacy; however, near-infrared (NIR) spectrometric screening coupled with high-dimensional principal component analysis (PCA) reveals complex, multidimensional inconsistencies within the commercially available product. Initial localized screening demonstrated significant intra-lot variability, with spectral data points forming a distinct toroidal pattern characteristic of cyclical oscillatory dynamics and an unstable mathematical average state. Extreme multidimensional outliers extending up to 5.6 standard deviations from the data centroid were observed diverging along multiple orthogonal trajectories, indicating that the intra-lot instability is driven by multiple independent physical and chemical mechanisms rather than a single processing failure. Expanding the evaluation to a comprehensive inter-lot analysis of 152 vials across 12 manufacturing lots confirmed that these inconsistencies persist at a systemic scale. The primary principal components divided the spectral library into two major, statistically distinct subpopulations, with asymmetric outlier distributions suggesting intermittent lapses in process control. Furthermore, projections in higher-order dimensions (PCs 7 through 9) isolated an entire manufacturing lot due to batch-level structural deviations possibly driven by trace moisture and aliphatic framework fluctuations. Nonparametric probability-density contour evaluations utilizing the FSOB algorithm and quantile-quantile (QQ) plots mathematically validated the presence of distinct subpopulations (r_tn=0.99, r_ts=0.88, <i>p</i>=0.02). Ultimately, these findings indicate that the manufacturing process is subjected to multiple, independent sources of instability, suggesting operations may intermittently fall outside a strict state of control.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2026 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrometric Assessment of Intralot and Interlot Variability in Mycophenolate Mofetil for Injection Using Near-Infrared Spectrometry and Nonparametric Subcluster Detection.","authors":"Uiyeol Yoon, Ayumi Tarianto, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Bailey Hall, Kyra Sharp, Madison Geib, Abby Wingate, Alexander Bacanurschi, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.33193629","DOIUrl":"https://doi.org/10.6084/m9.figshare.33193629","url":null,"abstract":"<p><p>Mycophenolate Mofetil for Injection is an antimetabolite immunosuppressant supplied as a sterile, lyophilized powder containing 500 mg of active drug per single-dose vial for intravenous administration. As a prodrug of mycophenolic acid, it selectively and reversibly inhibits inosine monophosphate dehydrogenase to block de novo guanosine nucleotide synthesis and suppress lymphocyte proliferation, carrying boxed warnings for embryofetal toxicity, serious opportunistic infections, and malignancies. Nondestructive Fourier transform near-infrared spectrometry coupled with principal component analysis and the Bootstrap Error-Adjusted Single-sample Technique was utilized to evaluate intralot and interlot spectral consistency across drug vials. Intra-lot analysis of a single 15-vial batch (Lot 2515203) revealed heterogeneity and outliers, with individual vials deviating up to 11.6 multidimensional standard deviations from the main cluster center. Interlot evaluation of a 464-vial spectral library spanning 18 distinct manufacturing lots demonstrated persistent two-group subclustering, with Principal Component 1 accounting for only 87.82% of total spectral variance. Nonparametric FSOB density estimation confirmed statistically significant subclustering across the multi-lot library (<i>p</i> = 0.02), dividing the sample set into two distinct groups (14.2% vs. 85.8%). While these findings do not establish active ingredient adulteration or excessive impurities, the observed intralot and interlot spectral variations indicate that the manufacturing process may have operated outside an ideal state of statistical process control, underscoring the value of PAT monitoring in health-system quality assurance.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2026 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Quality Screening of Intra-lot Variability of Acetazolamide Using Near-Infrared Spectrometry.","authors":"Uiyeol Yoon, Ayumi Tarianto, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Bailey Hall, Kyra Sharp, Madison Geib, Abby Wingate, Alexander Bacanurschi, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.31242187","DOIUrl":"10.6084/m9.figshare.31242187","url":null,"abstract":"<p><p>Acetazolamide for Injection, USP is a sterile, preservative-free carbonic anhydrase inhibitor primarily indicated for the treatment of acute mountain sickness, fluid volume overload associated with heart failure, and elevated intraocular pressure in glaucoma. This research utilized Fourier transform near-infrared spectrometry (FT-NIR) to evaluate the intra-lot variability of 12 vials of Mylan Institutional Acetazolamide 500 mg. While all sampled vials appeared visually identical as white to yellowish-white powders, FT-NIR analysis identified significant spectral heterogeneity, particularly in the range of 4200 to 5200 cm^-1. Statistical analysis using the Bootstrap Error-Adjusted Single-sample Technique (BEST) and Principal Component Analysis (PCA) identified vial 6 as a prominent statistical outlier. This vial exhibited a distinct absorbance peak at 4851 cm^-1, which was suggested to be a shift from a peak at 5173 cm^-1 and was positioned 4.03 standard deviations from the center of the lot cluster in multidimensional spectral hyperspace. These results suggest that the manufacturing process may have been operating outside of a state of process control. Given the ongoing national shortages of acetazolamide as of January 2026, such quality assurance screenings are critical for maintaining supply chain transparency and ensuring the reliability of medication used in evolving clinical protocols.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2026 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Quality Assessment of Ceftriaxone Using Near-Infrared Spectroscopy.","authors":"James T Isaacs, Philip J Almeter, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Eleonora Hasani, Uiyeol Yoon, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Joshua D Melson, Jeffrey W Reynolds, Ryan W Naseman, Thomas L Platt, Robert A Lodder","doi":"10.6084/m9.figshare.28593284","DOIUrl":"10.6084/m9.figshare.28593284","url":null,"abstract":"<p><p>Ceftriaxone for injection, USP is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is a white to yellowish crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The color of ceftriaxone sodium solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Each vial contains ceftriaxone sodium equivalent to 250 mg, 500 mg, 1 gram or 2 grams of ceftriaxone activity. Ceftriaxone sodium contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity. Intra-lot variability was detected in the spectra of 6 vials of ceftriaxone sampled from one lot. One of the vials was more than 8.3 multidimensional SDs away from the center of the cluster of the other 5 vials from the same lot, suggesting that the manufacturing process may not be in a state of control. Interlot variability was detected between two lots of the drug using a subcluster detection test (r_tn=0.9629, r_ts=0.9148, p=0.02).</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2025 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NIR Spectrometry Reveals Lack of Content Uniformity in Methylprednisolone Sodium Succinate.","authors":"James T Isaacs, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Uiyeol Yoon, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Madison Geib, Abby Wingate, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.30057982","DOIUrl":"10.6084/m9.figshare.30057982","url":null,"abstract":"<p><p>Methylprednisolone sodium succinate for injection, USP is an anti-inflammatory glucocorticoid. The active ingredient is methylprednisolone sodium succinate, which is the sodium succinate ester of methylprednisolone. The substance is a white or nearly white, odorless, hygroscopic, amorphous solid. It is highly soluble in water and alcohol, insoluble in chloroform, and only slightly soluble in acetone. This injectable form of the drug is indicated for the treatment of various conditions, including some allergic states, dermatologic, endocrine, gastrointestinal, hematologic, neoplastic, nervous system, ophthalmic, renal, respiratory, and rheumatic disorders. The analysis of a single lot of methylprednisolone sodium succinate revealed significant intra-lot variability in the near-infrared spectra. Differences were visually apparent in the absorbance peaks, particularly in the ranges of 4500 to 5000 cm^-1 and 6000 to 6500 cm^-1. Further examination of a zoomed-in region (7000 to 8500 cm^-1) showed two spectra that were statistically significant outliers, positioned at 4.4 and 5.9 standard deviations (SDs) from the center of the sample cluster. An analysis of a spectral library containing 242 vials of methylprednisolone sodium succinate from 26 different lots found significant interlot variability and statistically confirmed the presence of distinct subclusters. To statistically validate the visual findings, a subcluster detection algorithm was applied to the spectral data. The algorithm confirmed that two distinct groups exist within the spectral data. The measured correlation value (r_ts =0.8704) was below the 98% confidence level threshold (r_tn =0.9916), leading to the acceptance of the alternative hypothesis that more than one group is present.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2025 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12646679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-Infrared Spectrometry as a Tool for Screening Meropenem for Quality.","authors":"James T Isaacs, Philip J Almeter, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Eleonora Hasani, Uiyeol Yoon, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Joshua D Melson, Jeffrey W Reynolds, Eunice Relucio, Megan Bossle, Austin Lozier, Lindsey Long, Reagan Knight, Ryan W Naseman, Thomas L Platt, Robert A Lodder","doi":"10.6084/m9.figshare.28830275","DOIUrl":"10.6084/m9.figshare.28830275","url":null,"abstract":"<p><p>Meropenem for Injection, USP is a sterile, pyrogen-free, white to pale yellow crystalline powder and is supplied in vials containing sufficient meropenem to deliver 1 g for intravenous administration. The Drug Quality Task Force at the University of Kentucky has found variability in the near-infrared spectra of meropenem samples. The variability was found both within a lot (where one vial from six was 12.0 SDs from the other 5 vials) and between lots of the drug (where 8 vials were >3 SDs from the center of the library, and one of those was 6.1 SDs away from the center of the library). This variability was detected using a statistical analysis of the spectra that included principal component analysis (PCA) and the BEST metric. Inter-lot variability was assessed using a spectral library of 90 meropenem vials obtained from 15 lots of drug from the same manufacturer. The results suggest that the drug may have been manufactured while the manufacturing process was operating outside of a state of process control.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2025 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fourier Transform Near-Infrared Spectrometry Reveals Significant Inter-Lot Variability in Thyrotropin Alfa (Thyrogen^®) Quality.","authors":"Uiyeol Yoon, Ayumi Tarianto, Philip J Almeter, Eleonora Hasani, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Adler Crumrin, Jerod Smith, Spencer Pergrem, Ashton Plymale, Bailee Ramnes, Reagan Knight, Erin Vongchan, Samantha Schnabel, Bailey Hall, Kyra Sharp, Madison Geib, Abby Wingate, Alexander Bacanurschi, Ryan W Naseman, Robert A Lodder","doi":"10.6084/m9.figshare.30403540","DOIUrl":"10.6084/m9.figshare.30403540","url":null,"abstract":"<p><p>Thyrotropin alfa is a recombinant heterodimeric glycoprotein that serves as a highly purified form of human thyroid stimulating hormone (TSH). It is produced through recombinant DNA technology within a genetically modified Chinese hamster ovary (CHO) cell line. The molecule is structurally complex, consisting of two non-covalently linked subunits: an alpha subunit (92 amino acid residues) with two N-linked glycosylation sites, and a beta subunit (118 residues) containing one N-linked glycosylation site. The resulting amino acid sequence is identical to that of human pituitary TSH. Thyrotropin alfa is supplied as a sterile, non-pyrogenic, white to off-white lyophilized product, intended for intramuscular (IM) administration after reconstitution with Sterile Water for Injection, USP. Each vial of Thyrogen contains 1.1 mg thyrotropin alfa, 36 mg mannitol, 5.1 mg sodium phosphate, and 2.4 mg sodium chloride. The intralot analysis of the 12 vials sampled from lot EY0155 revealed significant differences in the drug product within the same manufacturing lot, as evidenced by both spectral plots and multivariate analysis. The visual differences were observed in the following wavenumber regions: 4000 to 5000 cm^-1, 5150 cm^-1, and the 6700 cm^-1 regions. The differences seen at 5150 cm^-1 are very likely a difference in moisture content. 25% of the vials were flagged as outliers, with vials appearing 3.3, 3.8, and 5.3 SDs from the center of the cluster of 12 vials. The interlot analysis of a spectral library containing 171 vials from 18 different lots of thyrotropin alfa demonstrated tremendous variability in the near-infrared absorption profiles across the samples. Obvious differences were observed in the spectra of the library at several wavenumber regions, including around 5900 and 6650 cm^-1. The ratio between two peak sizes between 5900 and 5950 cm^-1 was dramatically variable. Differences were also noted around 4250, 4400, and 4540 cm^-1, and from 4700 to 4800 cm^-1. Only one vial was an outlier, appearing 7.8 SDs away from the center of the library spectral cluster. Some literature suggests differences in the spectra of vials may reflect differences in the stability and efficacy of the drug.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2025 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12646678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Process Control Issues With Abatacept.","authors":"James T Isaacs, Philip J Almeter, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Lindsey M Long, Megan N Bossle, Smaran A Bhaktawara, Matthew F Warren, Austin M Lozier, Joshua D Melson, Savannah R Fraley, Eunice Hazzel L Relucio, Margaret A Felix, Jeffrey W Reynolds, Ryan W Naseman, Thomas L Platt, Robert A Lodder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Abatacept is a medication administered through intravenous infusion. It is supplied as a sterile, white, preservative-free, freeze-dried powder. Each vial of drug contains 250 mg abatacept, maltose, monobasic sodium phosphate, and sodium chloride for administration. Abatacept is a fusion protein consisting of the extracellular domain of CTLA-4 linked to the modified Fc portion of human immunoglobulin G1. It is produced using recombinant DNA technology. Abatacept is indicated for moderately to severely active rheumatoid arthritis in adults and polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. It can be used as monotherapy or in combination with other disease-modifying antirheumatic drugs or methotrexate. Inter-lot variability was detected in a library of 132 vials spread across 34 lots of abatacept-maltose for injection by the University of Kentucky Drug Quality Task Force. A subcluster detection test was run on 13 vials that were shown to be an outlier group (r_tn=0.9940, r_test=0.9551, r_lim=0.9865, <i>p</i>=0.02). Five of these vials individually appeared 4 or more standard deviations from the library cluster.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2024 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Near-Infrared Spectroscopy for Screening of Chlorothiazide Sodium Vials.","authors":"James T Isaacs, Philip J Almeter, Aaron N Hunter, Thomas A Lyman, Stephanie P Zapata, Bradley S Henderson, Seth A Larkin, Lindsey M Long, Megan N Bossle, Smaran A Bhaktawara, Matthew F Warren, Austin M Lozier, Joshua D Melson, Savannah R Fraley, Eunice Hazzel L Relucio, Margaret A Felix, Jeffrey W Reynolds, Ryan W Naseman, Thomas L Platt, Robert A Lodder","doi":"10.6084/m9.figshare.25773429","DOIUrl":"10.6084/m9.figshare.25773429","url":null,"abstract":"<p><p>Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO₂) is vital, with measurements ranging from 0.417×10^-5 to 1.012×10^-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO₂ boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2024 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11108027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}