{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:23:53Z","timestamp":1740165833062,"version":"3.37.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Proparacaine hydrochloric ophthalmic solution (0.5%) is widely used as ophthalmic anesthetic for short conjunctival and corneal procedures. In connection to this, present research work was conducted to investigate ocular toxicity of its probable degradation products (DPs), which were generated after treating drug with stressors mentioned under International Conference on Harmonization (ICH) guideline Q1A (R2).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Result<\/jats:title>\n                  <jats:p>The probable DPs were generated by placing drug under various stress conditions to generate similarity of the effect of stressor which drug supposed to face during its life cycle. The hydrolytic stress condition under acidic, basic and neutral environment formed two major DPs, while the drug was stable and did not generate any DP when subjected to oxidative, dry heat and photolytic stress. The separation of DPs was carried out using high performance liquid chromatographic system. The structural identification of DPs was carried out by subjecting degradation samples to liquid chromatography coupled with mass spectrometry. These DPs were screened using in-silico ocular toxicity prediction models Pub-SVM to predict their potential to cause irritation\/corrosion to eye.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The DPs identified were DP 1 (2-(diethyl amino) ethanol) and DP 2 (3-amino-4-propoxybenzoic acid). The in-silico ocular toxicity study predicted that DP 1 has potential of eye corrosion (EC) and eye irritation (EI), whereas DP 2 has a potential EI. The drug was found safe and devoid of any EC and EI potential.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/chromsci\/bmac039","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T19:09:55Z","timestamp":1650913795000},"page":"393-401","source":"Crossref","is-referenced-by-count":0,"title":["Prediction of Ocular Toxicity of Potential Degradation Products of Proparacaine Hydrochloride Subjected under ICH Recommended Stress Conditions"],"prefix":"10.1093","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-4559","authenticated-orcid":false,"given":"Anand","family":"Mahajan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis , Goa College of Pharmacy, 18th June Road, Panaji 403001, Goa, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis , Goa College of Pharmacy, 18th June Road, Panaji 403001, Goa, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghuvir","family":"Pissurlenkar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry , Goa College of Pharmacy, 18th June Road, Panaji 403001, Goa, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adison","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis , Goa College of Pharmacy, 18th June Road, Panaji 403001, Goa, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amol","family":"Tagalpallewar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics , School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Pune 411038, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"2023042616353433500_ref1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0099-5428(08)60350-0","article-title":"Proparacaine hydrochloride","volume":"6","author":"Whigan","year":"1977","journal-title":"Analytical Profiles of Drug Substances"},{"key":"2023042616353433500_ref2","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-71110-7_2","volume-title":"The action of local anesthetics on ion channels of excitable tissues","author":"Strichartz","year":"1987"},{"volume-title":"vol 1","year":"2013","first-page":"4929","key":"2023042616353433500_ref3"},{"volume-title":"vol 1","year":"2013","first-page":"p1897","key":"2023042616353433500_ref4"},{"issue":"8","key":"2023042616353433500_ref5","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1517\/17425255.2013.794219","article-title":"Toxicity of topical ophthalmic anesthetics","volume":"9","author":"Patel","year":"2013","journal-title":"Expert Opinion on Drug Metabolism & Toxicology"},{"issue":"6","key":"2023042616353433500_ref6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1517\/14740338.6.6.637","article-title":"Toxicities of topical ophthalmic anesthetics","volume":"6","author":"McGee","year":"2007","journal-title":"Expert Opinion on Drug Safety"},{"issue":"5","key":"2023042616353433500_ref7","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.jemermed.2015.06.069","article-title":"The safety of topical anesthetics in the treatment of corneal abrasions: a review","volume":"49","author":"Swaminathan","year":"2015","journal-title":"The Journal of Emergency Medicine"},{"issue":"3","key":"2023042616353433500_ref8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3109\/15569527.2012.744758","article-title":"Topical anesthetic eye drops abuse: are we aware of the danger?","volume":"32","author":"Erdem","year":"2013","journal-title":"Cutaneous and Ocular Toxicology"},{"issue":"6","key":"2023042616353433500_ref9","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1444-0938.2012.00728.x","article-title":"Topical ocular anaesthetic abuse in a contact lens wearer: a case of microbial keratitis","volume":"95","author":"Matti","year":"2012","journal-title":"Clinical & Experimental Optometry"},{"issue":"1","key":"2023042616353433500_ref10","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/ICO.0b013e3181e458af","article-title":"Topical anesthetic abuse keratitis secondary to floppy eyelid syndrome","volume":"30","author":"Goldich","year":"2011","journal-title":"Cornea"},{"issue":"1","key":"2023042616353433500_ref11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/ICL.0b013e318193a48d","article-title":"An atypical presentation of acanthamoeba keratitis in a patient with keratoconus treated briefly with topical anesthetic","volume":"35","author":"Eric","year":"2009","journal-title":"Eye & Contact Lens"},{"issue":"4","key":"2023042616353433500_ref12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1055\/s-2007-962933","article-title":"Clinical findings in patients with topical anaesthetic abuse keratitis: a report of five cases","volume":"224","author":"Katsimpris","year":"2007","journal-title":"Klinische Monatsbl\u00e4tter f\u00fcr Augenheilkunde"},{"key":"2023042616353433500_ref13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tox.2014.11.003","article-title":"An overview of current techniques for ocular toxicity testing","volume":"327","author":"Wilson","year":"2015","journal-title":"Toxicology"},{"key":"2023042616353433500_ref14","article-title":"High performance liquid chromatography method for separating proparacaine hydrochloride intermediate IV from other intermediates","volume":"19","author":"Yan","year":"2012","journal-title":"Chinese Patent CN102721775A"},{"issue":"S1","key":"2023042616353433500_ref15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1365\/s10337-007-0266-y","article-title":"Development and validation of an HPLC\u2013UV\u2013Vis method for the determination of proparacaine in human aqueous humour","volume":"66","author":"Dincel","year":"2007","journal-title":"Chromatographia"},{"issue":"S1","key":"2023042616353433500_ref16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1365\/s10337-007-0275-x","article-title":"An experimental design approach to selecting the optimum LC conditions for the determination of local anaesthetics","volume":"66","author":"Dincel","year":"2007","journal-title":"Chromatographia"},{"issue":"13","key":"2023042616353433500_ref17","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1007\/s00216-015-8574-9","article-title":"A simple method for the subnanomolar quantitation of seven ophthalmic drugs in the rabbit eye","volume":"407","author":"Latreille","year":"2015","journal-title":"Analytical and Bioanalytical Chemistry"},{"issue":"7","key":"2023042616353433500_ref18","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2116\/analsci.17P589","article-title":"Determination of ophthalmic drug proparacaine using multi walled carbon nanotube paste electrode by square wave stripping voltammetry","volume":"34","author":"Ersin","year":"2018","journal-title":"Analytical Sciences"},{"key":"2023042616353433500_ref19","doi-asserted-by":"crossref","first-page":"113497","DOI":"10.1016\/j.jpba.2020.113497","article-title":"Identification, synthesis and structural confirmation of process-related impurities in proparacaine hydrochloride","volume":"190","author":"Yang","year":"2020","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"volume-title":"Proceedings of the International Conference on Harmonization","year":"2003","author":"ICH Q1A (R2)","key":"2023042616353433500_ref20"},{"volume-title":"International Conference on Harmonization","year":"1996","author":"ICH Q 1B","key":"2023042616353433500_ref21"},{"volume-title":"Proceedings of the International Conference on Harmonization IFMPA","year":"2005","author":"ICHQ2 (R1)","key":"2023042616353433500_ref22"},{"issue":"11","key":"2023042616353433500_ref23","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.1039\/C6RA25267B","article-title":"In silico prediction of serious eye irritation or corrosion potential of chemicals","volume":"7","author":"Wang","year":"2017","journal-title":"RSC Advances."}],"container-title":["Journal of Chromatographic Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/chromsci\/article-pdf\/61\/4\/393\/50071914\/bmac039.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/chromsci\/article-pdf\/61\/4\/393\/50071914\/bmac039.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T16:37:16Z","timestamp":1682527036000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/chromsci\/article\/61\/4\/393\/6583207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,10]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,5,10]]},"published-print":{"date-parts":[[2023,4,24]]}},"URL":"https:\/\/doi.org\/10.1093\/chromsci\/bmac039","relation":{},"ISSN":["0021-9665","1945-239X"],"issn-type":[{"type":"print","value":"0021-9665"},{"type":"electronic","value":"1945-239X"}],"subject":[],"published-other":{"date-parts":[[2023,4]]},"published":{"date-parts":[[2022,5,10]]}}}