Contact in contextPub Date : 2024-01-01DOI: 10.6084/m9.figshare.25773429
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
{"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 (scCO<sub>2</sub>) is vital, with measurements ranging from 0.417×10<sup>-5</sup> to 1.012×10<sup>-5</sup> mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO<sub>2</sub> 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}
Contact in contextPub Date : 2023-01-01DOI: 10.6084/m9.figshare.24846285
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
{"title":"Assessment of Vecuronium Quality Using Near-Infrared Spectrometry.","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.24846285","DOIUrl":"10.6084/m9.figshare.24846285","url":null,"abstract":"<p><p>This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378928","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}
Contact in contextPub Date : 2023-01-01DOI: 10.6084/m9.figshare.23317136
James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Claire McGuire, Robert A Lodder
{"title":"Spectrometric Analysis of Dantrolene Sodium.","authors":"James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Claire McGuire, Robert A Lodder","doi":"10.6084/m9.figshare.23317136","DOIUrl":"https://doi.org/10.6084/m9.figshare.23317136","url":null,"abstract":"<p><p>Dantrolene sodium is a direct-acting skeletal muscle relaxant. Dantrolene sodium for injection is indicated, along with suitable supportive measures, for the management of sudden, severe hypermetabolism of skeletal muscle typical of malignant hyperthermia crises in patients of any age. The formulation scanned in this work was designed to be injected intravenously. Intra-lot and inter-lot variability in the spectra of REVONTO<sup>™</sup> (dantrolene sodium) was measured in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Spectra of 69 vials from lot 20REV01A contained two groups (n<sub>1</sub>=56 vials, n<sub>2</sub>=13 vials) when scanned with an FTNIR. The two groups of spectra in lot 20REV01A were found to be 66.7 SDs apart using a subcluster detection test, suggesting that the two groups were manufactured differently. As a result, all available samples of dantrolene were examined. A library of spectra of 141 vials of dantrolene from 4 lots were found to contain 3 separate groups, also suggesting that different vials contain different materials.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327630/pdf/nihms-1907182.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167230","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}
James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder
{"title":"Nonparametric Subcluster Detection in Large Hyperspaces.","authors":"James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This assessment of subcluster detection in analytical chemistry offers a nonparametric approach to address the challenges of identifying specific substances (molecules or mixtures) in large hyperspaces. The paper introduces the concept of subcluster detection, which involves identifying specific substances within a larger cluster of similar samples. The BEST (Bootstrap Error-adjusted Single-sample Technique) metric is introduced as a more accurate and precise method for discriminating between similar samples compared to the MD (Mahalanobis distance) metric. The paper also discusses the challenges of subcluster detection in large hyperspaces, such as the curse of dimensionality and the need for nonparametric methods. The proposed nonparametric approach involves using a kernel density estimator to determine the probability density function of the data and then using a quantile-quantile algorithm to identify subclusters. The paper provides examples of how this approach can be used to analyze small changes in the near-infrared spectra of drug samples and identifies the benefits of this approach, such as improved accuracy and precision.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302418","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}
Contact in contextPub Date : 2023-01-01DOI: 10.6084/m9.figshare.23573532
Margaret Felix, James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder
{"title":"Variability in Content of Hydrocortisone Sodium Succinate.","authors":"Margaret Felix, James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder","doi":"10.6084/m9.figshare.23573532","DOIUrl":"https://doi.org/10.6084/m9.figshare.23573532","url":null,"abstract":"<p><p>SOLU-CORTEF<sup>Ⓡ</sup> Sterile Powder is a type of anti-inflammatory glucocorticoid that contains hydrocortisone sodium succinate as its active ingredient. It can be administered intravenously or intramuscularly, and comes in several packages including 100 mg plain vials without diluent. The diluent, which is part of the ACT-O-VIAL system, contains only Water for Injection and no preservatives. The pH of each formula is adjusted with sodium hydroxide to ensure it falls within the specified range of 7 to 8 after reconstitution. Intralot variability was detected in lot GA6092. Measuring in the PC subspace using just PCs 4, 5 and 6, vial 12 plots 4.2 BEST SDs from the center of the cluster, and vial 7 is 3.7 SDs from the center. Vial 18 appears 3.1 SDS from the center of the cluster (3/18, 17%). Interlot variability was also found in the spectral library (lots GA6092, GK7048, GM6839, GR8925, FL8062, FN6860, FR1914, and FR5098) containing the spectra of 126 hydrocortisone sodium succinate vials.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10437148/pdf/nihms-1911816.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049458","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}
Contact in contextPub Date : 2023-01-01DOI: 10.6084/m9.figshare.21971213
James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Humza Anwar, Robert A Lodder
{"title":"Spectral Intra-Lot and Inter-Lot Variability in Carfilzomib.","authors":"James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Humza Anwar, Robert A Lodder","doi":"10.6084/m9.figshare.21971213","DOIUrl":"https://doi.org/10.6084/m9.figshare.21971213","url":null,"abstract":"<p><p>Carfilzomib is a prescription injectable drug approved for use by the FDA as an antineoplastic agent, part of a drug class of medications known as proteasome inhibitors, and used to stop and slow the growth and progression of cancer cells within the body. The drug is approved as an agent to treat multiple myeloma. It is provided as a single-use vial that contains 60 mg of carfilzomib as a sterile, white to off-white lyophilized cake or powder. Intra-lot and inter-lot variability in the spectra of carfilzomib vials was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). One of 12 vials of lot 1143966 manufactured for Onyx Pharmaceuticals, Inc. appeared 4.7 multidimensional standard deviations (SDs) from the other 11 vials in a 3-D space formed by the first 3 principal components, which captured 81% of the total spectral variation. Spectra of 168 vials from 18 lots in the spectral library formed two groups in the 3-D space formed by the first 3 principal components. One group contained 155 vials and the other group contained 13 vials. The 2 groups had different locations and scales using a subcluster detection test at <i>p=0.02</i>.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062383/pdf/nihms-1877094.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335697","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}
Contact in contextPub Date : 2023-01-01Epub Date: 2023-06-20DOI: 10.6084/m9.figshare.23524530
James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Cristian Samano-Garcia, Robert A Lodder
{"title":"Quality Variations in Thyrotropin Alfa.","authors":"James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Cristian Samano-Garcia, Robert A Lodder","doi":"10.6084/m9.figshare.23524530","DOIUrl":"10.6084/m9.figshare.23524530","url":null,"abstract":"<p><p>Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen<sup>®</sup> was detected in the Drug Quality Study (DQS). The vials fell into two distinct groups (r<sub>tst</sub> = 0.90, r<sub>lim</sub>= 0.98, <i>p</i>=0.02). In addition, one vial of the 30 (3%) appeared 4.7 multidimensional SDs from all of the other vials, suggesting that it also represents a different material.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"2023 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312997/pdf/nihms-1910673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9806918","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}
Contact in contextPub Date : 2022-01-01Epub Date: 2022-09-14DOI: 10.6084/m9.figshare.21109093
James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder
{"title":"Spectrometric Analysis of Process Variations in Remifentanil.","authors":"James T Isaacs, Philip J Almeter, Bradley S Henderson, Aaron N Hunter, Thomas L Platt, Robert A Lodder","doi":"10.6084/m9.figshare.21109093","DOIUrl":"https://doi.org/10.6084/m9.figshare.21109093","url":null,"abstract":"<p><p>ULTIVA® (remifentanil hydrochloride) is a sterile, nonpyrogenic, preservative-free, white to off-white lyophilized powder for intravenous (IV) administration after reconstitution and dilution. Each vial contains 1, 2, or 5 mg of remifentanil base; 15 mg glycine; and hydrochloric acid to buffer the solutions to a nominal pH of 3 after reconstitution. ULTIVA® is a μ-opioid agonist with rapid onset and peak effect, and short duration of action. Intra-lot and inter-lot variability in the spectra of ULTIVA® was measured in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). In 6 vials sampled, 1 came from lot 220453F while 5 came from lot 30020BF. The 1 vial sampled from lot 220453F appeared 122 multidimensional SDs from the other vials from lot 30020BF, suggesting that it represents a different formulation or material. Consequently, additional spectra from other lots were analyzed. Spectra of 90 vials from 9 lots in the spectral library contained vials that were outside the main group (50.3 SDs using a subcluster detection test), suggesting that the 35 library vials (39% of the total) contain different materials from the other 55 vials.</p>","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520611/pdf/nihms-1836546.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391844","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}
Contact in contextPub Date : 2022-01-01DOI: 10.6084/m9.figshare.19071704
James T. Isaacs, Philip J. Almeter, Bradley S. Henderson, Aaron N. Hunter, Thomas L. Platt, R. Lodder
{"title":"FTNIR Spectrometry of Micafungin Sodium Quality.","authors":"James T. Isaacs, Philip J. Almeter, Bradley S. Henderson, Aaron N. Hunter, Thomas L. Platt, R. Lodder","doi":"10.6084/m9.figshare.19071704","DOIUrl":"https://doi.org/10.6084/m9.figshare.19071704","url":null,"abstract":"Intra-lot and inter-lot variability in the spectra of micafungin was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Two vials of 6 vials sampled from Fresenius Kabi lot ACP106 appeared 7.9 and 14.0 standard deviations (SDs) from the center of the rest of the vials on the DQS FTNIR screening assay. Spectra of 48 vials from 7 lots in the library showed 2 outliers at 8.3 and 9.8 SDs from the center of the rest of the library, suggesting they represent different material.","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91155992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Contact in contextPub Date : 2022-01-01DOI: 10.6084/m9.figshare.19217478
James T. Isaacs, Philip J. Almeter, Bradley S. Henderson, Aaron N. Hunter, Thomas L. Platt, R. Lodder
{"title":"Lack of Content Uniformity in MMR Vaccine.","authors":"James T. Isaacs, Philip J. Almeter, Bradley S. Henderson, Aaron N. Hunter, Thomas L. Platt, R. Lodder","doi":"10.6084/m9.figshare.19217478","DOIUrl":"https://doi.org/10.6084/m9.figshare.19217478","url":null,"abstract":"The measles, mumps, and rubella (MMR) vaccine is a vaccine used to prevent measles, mumps, and rubella (German measles). The vaccine is mandated for children to attend public school in nearly all US states. However, measles cases have been increasing in the past decade, and quality problems have recently been noted by the US Food and Drug Administration (FDA) with the vaccine manufacturer. Intra-lot and inter-lot variability in the spectra of MMR (measles, mumps, and rubella) vaccine was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Six vials of 12 (50%) sampled from Merck lot U006488 appeared 14.5 SDs from the other vials on a subcluster detection test, suggesting that they represent different material. Spectra of 198 vials from 12 lots in the spectral library contained 140 vials in one tight ellipsoidal group, and 58 vials (30%) were outside that group (39.7 SDs using a subcluster detection test), suggesting that the library vials also contain differing materials.","PeriodicalId":72698,"journal":{"name":"Contact in context","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75925071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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