{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:27:21Z","timestamp":1787236041730,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807112702005"],"award-info":[{"award-number":["JCYJ20230807112702005"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Isoniazid is an irreplaceable first\u2010line anti\u2010tuberculosis drug. Its synthesis requires hydrazine as a starting material, which is classified as a Class 2 genotoxic impurity according to the ICH M7 guideline. Consequently, there is a risk of introducing potential genotoxic impurities (PGIs) containing hydrazine\u2010related alerting structural during production. This study employed a systematic approach to assess the risks of PGIs in isoniazid and developed a novel LC\u2010MS\/MS method for accurate control and quantification of these impurities. First, candidate impurities were preliminarily predicted using quantitative structure\u2013activity relationship (QSAR) systems based on expert rule and statistics. Subsequently, acceptable impurity limits were established based on the prediction results. Finally, an LC\u2010MS\/MS method was developed to quantify the selected PGIs. The results indicated that the impurities were classified as Class 3 (3,5\u2010bis(4\u2010pyridyl)\u20104\u2010amino\u20101,2,4\u2010triazole), Class 4 (benzohydrazide, picolinohydrazide, and nicotinohydrazide), and Class 5 (3,6\u2010di(4\u2010pyridyl)\u20101,4\u2010dihydro\u20101,2,4,5\u2010tetrazine). According to the ICH Q3B guidelines and the threshold of toxicological concern (TTC) based on the duration of administration, the limits of Class 4 and 5 impurities were set at 0.1%, and the limit of Class 3 impurities was set at 0.0066%. The established method demonstrated excellent linearity (\n                    <jats:italic>r<\/jats:italic>\n                    &gt; 0.999) within the range of 0.2\u201025\u00a0ng\/mL. And good recoveries were observed in the range of 88.1%\u2013113.0%. The method was successfully applied to quantify impurities in 77 batches of isoniazid injections, all of which complied with the established acceptance limits. This universal strategy enhances quality control of isoniazid formulations, ensuring clinical safety through robust impurity assessment and validated analytical methodology.\n                  <\/jats:p>","DOI":"10.1002\/jssc.70235","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:10:58Z","timestamp":1753960258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Universal Strategy for Evaluation and Quantification of Potential Genotoxic Impurities of Hydrazine Derivatives in Isoniazid Injection"],"prefix":"10.1002","volume":"48","author":[{"given":"Changhong","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Institute for Drug Control  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Yin","sequence":"additional","affiliation":[{"name":"Shenzhen Institute for Drug Control  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9499-8615","authenticated-orcid":false,"given":"Ran","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food and Drug Shenzhen Polytechnic University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.09.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202300214"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202200225"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201800623"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.114630"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2024.125902"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27134129"},{"key":"e_1_2_9_9_1","volume-title":"Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk","author":"ICH","year":"2023"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/separations10030145"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202100136"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.11.039"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.7b00223"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00771896"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2006.10.013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(89)90037-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27144437"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2013.851691"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2022.105245"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10629369908039182"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA02345E"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.12.006"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300095f"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2024.110828"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00234"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202300125"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5336"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2016.07.081"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.114974"},{"key":"e_1_2_9_30_1","volume-title":"European Pharmacopoeia (Ph. Eur. 11.3)","author":"European Directorate for the Quality of Medicines","year":"2023"},{"key":"e_1_2_9_31_1","volume-title":"Q2(R2): Validation of Analytical Procedures","author":"ICH","year":"2023"},{"key":"e_1_2_9_32_1","volume-title":"Q3B (R2): Impurities in New Drug Products","author":"ICH","year":"2006"},{"key":"e_1_2_9_33_1","unstructured":"\u201cFDA Label: Isoniazid Injection \u201dFDA 2022 https:\/\/nctr\u2010crs.fda.gov\/fdalabel\/services\/spl\/set\u2010ids\/77795c31\u20101cdf\u20104a20\u2010b4a1\u2010cd15f5b310f1\/spl\u2010doc?hl=isoniazid."}],"container-title":["Journal of Separation Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.70235","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:42:21Z","timestamp":1764664941000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jssc.70235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/jssc.70235"],"URL":"https:\/\/doi.org\/10.1002\/jssc.70235","archive":["Portico"],"relation":{},"ISSN":["1615-9306","1615-9314"],"issn-type":[{"value":"1615-9306","type":"print"},{"value":"1615-9314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"2025-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70235"}}