{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:13:41Z","timestamp":1786122821291,"version":"build-2736575974"},"reference-count":20,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cariprazine (CAR) and lurasidone (LUR) are antipsychotic drugs used to treat schizophrenia. These drugs are relatively new in clinical practice, and there is a need to optimise and develop analytical methods for their determination in various biological matrices for biomedical analysis. To date, the detection of these drugs has been performed in serum and urine, but there are no methods for determining these drugs in saliva. In the first part of this study, various chromatographic systems were compared using high-performance liquid chromatography with diode array detection (HPLC-DAD) or coupled with quadrupole\u2013linear ion trap tandem mass spectrometry (HPLC-QTRAP-MS\/MS), taking into account the retention of tested compounds, system efficiency and peak symmetry. Next, a simple, rapid, and sensitive HPLC-QTRAP-MS\/MS method has been developed for the determination of CAR and LUR in human serum, urine, and, for the first time, in saliva samples. Solid-phase extraction (SPE) was used for sample pre-treatment. Quantifications were carried out using a Polar RP column with a mobile phase consisting of acetonitrile and a formate buffer at pH 4.0 in gradient mode. The method was successfully applied for the determination of CAR and LUR in biological samples obtained from psychiatric patients. The findings suggest that saliva may be a non-invasive alternative for the quantification of free levels of investigated drugs, although further studies are required to clarify its relationship with plasma concentrations.<\/jats:p>","DOI":"10.3390\/ijms27167090","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:44:53Z","timestamp":1786103093000},"page":"7090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Chromatographic Optimisation to Bioanalysis: HPLC System Comparison and HPLC\u2013QTRAP\u2013MS\/MS Determination of Cariprazine and Lurasidone in Human Serum, Urine, and Saliva"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-7056","authenticated-orcid":false,"given":"Karol","family":"Wr\u00f3blewski","sequence":"first","affiliation":[{"name":"Laboratory of Commercial and Non-Commercial Clinical Trials, University of Rzesz\u00f3w, Kopisto 2a, 35-959 Rzesz\u00f3w, Poland"},{"name":"Laboratory of Metabolic Processes and Chromatographic Analyses, Natural and Medical Center for Innovative Research, University of Rzesz\u00f3w, Kopisto 2a, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-3217","authenticated-orcid":false,"given":"Anna","family":"Petruczynik","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Medical University of Lublin, Chod\u017aki 4a, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Rz\u0105d","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuropsychiatry, Medical University of Lublin, G\u0142uska 2, 20-439 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-795X","authenticated-orcid":false,"given":"Hanna","family":"Karaku\u0142a-Juchnowicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuropsychiatry, Medical University of Lublin, G\u0142uska 2, 20-439 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.euroneuro.2019.06.008","article-title":"Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone","volume":"29","author":"Corponi","year":"2019","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115740","DOI":"10.1016\/j.jpba.2023.115740","article-title":"Volumetric absorptive microsampling for the therapeutic drug monitoring of psychiatric patients treated with cariprazine","volume":"236","author":"Vitagliano","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.neuint.2011.07.002","article-title":"Cariprazine (RGH-188), a potent D3\/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents","volume":"59","author":"Kiss","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/22297928.2023.2242857","article-title":"Development of RP-HPLC based analytical method for determination of cariprazine hydrochloride in bulk drug and pharmaceutical dosage form using Box-Behnken statistical design","volume":"13","author":"Chiprikar","year":"2023","journal-title":"Anal. Chem. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"124523","DOI":"10.1016\/j.jchromb.2025.124523","article-title":"A dilute\u2013and\u2013shoot LC\u2013MS\/MS determination of low\u2013dosage third\u2013generation antipsychotics and their metabolites in urine using an ultra-short column","volume":"1255","author":"Kim","year":"2025","journal-title":"J. Chromatogr. B"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120588","DOI":"10.1016\/j.jad.2025.120588","article-title":"The impact of CYP3A4 rs2242480 on oral lurasidone: A population pharmacokinetic model and exposure-efficacy analysis in Chinese bipolar depression patients","volume":"394","author":"Dai","year":"2026","journal-title":"J. Affect. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115833","DOI":"10.1016\/j.biopha.2023.115833","article-title":"The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone","volume":"168","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"172933","DOI":"10.1016\/j.pbb.2020.172933","article-title":"Antipsychotic lurasidone: Behavioural and pharmacokinetic data in C57BL\/6 mice","volume":"194","author":"Percelay","year":"2020","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100427","DOI":"10.1016\/j.rechem.2022.100427","article-title":"Quantification of panel of most potent antipsychotic medicines by high throughput UPLC method","volume":"4","author":"Jebaliya","year":"2022","journal-title":"Results Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123279","DOI":"10.1016\/j.jchromb.2022.123279","article-title":"Qualitative and semi-quantitative screening of selected psychoactive drugs in blood: Usefulness of liquid chromatography\u2014Triple quadrupole and quadrupole time-of-flight mass spectrometry in routine toxicological analyses","volume":"1206","author":"Degreef","year":"2022","journal-title":"J. Chromatogr. B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e32274","DOI":"10.1016\/j.heliyon.2024.e32274","article-title":"UPLC-MS\/MS determination of 71 neuropsychotropic drugs in human serum","volume":"10","author":"Jin","year":"2024","journal-title":"Heliyon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/00498254.2025.2498699","article-title":"Degradation studies on lurasidone hydrochloride using validated reverse phase HPLC and LC\u2013MS\/MS","volume":"55","author":"Kadam","year":"2025","journal-title":"Xenobiotica"},{"key":"ref_13","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (2025, November 30). ICH Harmonised Guideline Bioanalytical Method Validation M10. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-guideline-m10-bioanalytical-method-validation-step-5_en.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Turkovi\u0107, L., Bo\u010dkor, L., Ekpenyong, O., Silovski, T., Lovri\u0107, M., Crnkovi\u0107, S., Nigovi\u0107, B., and Serti\u0107, M. (2022). Development and Validation of a Novel LC-MS\/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050614"},{"key":"ref_15","unstructured":"European Medicines Agency (2025, November 30). Guideline on Bioanalytical Method Validation. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-0043-116492","article-title":"Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017","volume":"51","author":"Hiemke","year":"2018","journal-title":"Pharmacopsychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.jpba.2007.12.016","article-title":"Sensitive LC-MS\/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine","volume":"48","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wr\u00f3blewski, K., Zheng, Y., and Yue, X. (2025). Editorial: Non-invasive methods in drug metabolism and transport: Insights from biological samples to oral administration. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1735743"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wr\u00f3blewski, K., Petruczynik, A., Tuzimski, T., Przygodzka, D., Buszewicz, G., Ko\u0142odziejczyk, P., and Tutka, P. (2019). Comparison of Various Chromatographic Systems for Analysis of Cytisine in Human Serum, Saliva and Pharmaceutical Formulation by HPLC with Diode Array, Fluorescence or Mass Spectrometry Detection. Molecules, 24.","DOI":"10.3390\/molecules24142580"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1515\/chem-2019-0152","article-title":"Optimization of chromatographic systems for analysis of selected psychotropic drugs and their metabolites in serum and saliva by HPLC in order to monitor therapeutic drugs","volume":"17","author":"Petruczynik","year":"2019","journal-title":"Open Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:46:06Z","timestamp":1786103166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":20,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167090"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167090","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}