{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:45:44Z","timestamp":1792431944021,"version":"4.5.0"},"reference-count":42,"publisher":"The Royal Society","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["R. Soc. open sci."],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:p>\n                    Angiotensin-converting enzyme inhibitors are one of the most widely used anti-hypertensive drugs which are used to reduce hypertension. In 2018, the United States Food and Drug Administration together with the European Medicine Agency declared the presence of carcinogenic nitrosamine impurities such as nitrosodiethylamine (NDEA) in some of the products, including valsartan (VLS) and losartan (LOS), and drugs' recall procedures were started. Thus, they should be controlled to be below the acceptable cancer risk level to ensure safety of the pharmaceutical products. Therefore, sensitive and reliable analytical methods were required for detection and quantitation of NDEA in bulk and finished drug products. Green analytical chemistry has received great interest to minimize the amount of organic solvents consumed without loss in chromatographic performance. A green and sensitive HPLC method was developed for the determination of NDEA in LOS and VLS using mobile phase of 0.02 M ammonium acetate adjusted to pH 7.2 and ethanol in gradient manner. Limits of detection and limits of quantification for NDEA were estimated to be 0.2 and 0.5 \u00b5g ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    , respectively. The standardized limits of NDEA impurity in drug substances were set as 0.56 ppm, which indicates the feasibility of its determination by the proposed conventional method without need for expensive instrumentations (e.g. MS\/MS detectors) that are not found in most pharmaceutical quality control laboratories.\n                  <\/jats:p>","DOI":"10.1098\/rsos.220250","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T03:11:05Z","timestamp":1654053065000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Cost-effective, green HPLC determination of losartan, valsartan and their nitrosodiethylamine impurity: application to pharmaceutical dosage forms"],"prefix":"10.1098","volume":"9","author":[{"given":"Soad S.","family":"Abd El-Hay","sequence":"first","affiliation":[{"name":"Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Elhenawee","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Maged","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Sinai University, El-Areesh, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7421-1220","authenticated-orcid":true,"given":"Adel Ehab","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Port-Said University, Port-Said, Egypt"},{"name":"Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2022,6]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1613481"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202000429"},{"key":"e_1_3_6_4_2","first-page":"1","article-title":"Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy","volume":"7","author":"Law M","year":"2003","unstructured":"Law M, Wald N, Morris J. 2003 Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol. Assess. (Winchester, England) 7, 1-94. (doi:10.3310\/hta7010)","journal-title":"Health Technol. Assess. (Winchester, England)"},{"key":"e_1_3_6_5_2","first-page":"429","article-title":"Angiotensin-converting enzyme inhibitors in hypertension: a review","volume":"5","author":"Salvetti A","year":"1985","unstructured":"Salvetti A, Pedrinelli R, Arzilli F, Abdel-Haq B, Magagna A, Lucarini A, Graziadei L, Nuccorini A, Taddei S. 1985 Angiotensin-converting enzyme inhibitors in hypertension: a review. Int. J. Clin. Pharmacol. Res. 5, 429-438.","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.07.026"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02120"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.180025"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2020.1788375"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.04.035"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000000323"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-016-9726-2"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2021.119748"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10337-017-3425-9"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2013.04.012"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/MGC-160213"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2020.105594"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.190310"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40543-020-00254-2"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/bkcs.12085"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113460"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.38212\/2224-6614.1063"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c00982"},{"key":"e_1_3_6_24_2","unstructured":"USFDA. 2019 Liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for the determination of six nitrosamine impurities in ARB drugs . US Food and Drug Administration. See https:\/\/www.fda.gov\/media\/125478\/download."},{"key":"e_1_3_6_25_2","first-page":"541","article-title":"Development and validation of four nitrosamine impurities determination method in medicines of valsartan, losartan, and irbesartan with HPLC-MS\/MS (APCI)","volume":"20","author":"Khorolskiy M","year":"2021","unstructured":"Khorolskiy M, Ramenskaya G, Vlasov A, Perederyaev O, Maslennikova N. 2021 Development and validation of four nitrosamine impurities determination method in medicines of valsartan, losartan, and irbesartan with HPLC-MS\/MS (APCI). Iranian J. Pharmaceut. Res. 20, 541-552.","journal-title":"Iranian J. Pharmaceut. Res."},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.04.049"},{"key":"e_1_3_6_27_2","first-page":"31","article-title":"Screening of nitrosamine impurities in sartan pharmaceuticals by GC-MS\/MS","volume":"12","author":"Chang SH","year":"2021","unstructured":"Chang SH, Ho HY, Zang CZ, Hsu YH, Lin MC, Tseng SH, Wang DY. 2021 Screening of nitrosamine impurities in sartan pharmaceuticals by GC-MS\/MS. Mass Spectrometry Lett. 12, 31-40.","journal-title":"Mass Spectrometry Lett."},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.113960"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2012.03.013"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-021-03469-3"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/jaoacint\/qsab100"},{"key":"e_1_3_6_32_2","unstructured":"ICH. 2005 ICH guidelines for validation of analytical procedures: text and methodology Q2 (R1) pp. 11\u201312. Geneva Switzerland: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use."},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27072330"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e01518"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-020-01897-z"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-020-01981-4"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2006.07.074"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2009.07.022"},{"key":"e_1_3_6_39_2","unstructured":"Merck. 2021 Ammonium acetate . See https:\/\/www.sigmaaldrich.com\/EG\/en\/product\/aldrich\/240192 (accessed December 2021)."},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2018.01.013"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c01887"},{"key":"e_1_3_6_42_2","unstructured":"United Nations Economic Commission for Europe. 2015 Globally harmonized system of classification and labelling of chemicals (GHS). Copyright Law of the United States."},{"key":"e_1_3_6_43_2","doi-asserted-by":"crossref","unstructured":"Abd El-Hay SS Elhenawee M Maged K Ibrahim AE. 2022 Cost-effective green HPLC determination of losartan valsartan and their nitrosodiethylamine impurity; application to pharmaceutical dosage-forms. FigShare . (doi:10.6084\/m9.figshare.c.6011541)","DOI":"10.2139\/ssrn.3979001"}],"container-title":["Royal Society Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.220250","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsos.220250","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.220250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T06:53:01Z","timestamp":1682664781000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsos.220250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1098\/rsos.220250"],"URL":"https:\/\/doi.org\/10.1098\/rsos.220250","relation":{},"ISSN":["2054-5703"],"issn-type":[{"value":"2054-5703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"2022-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"220250"}}