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The endogenous compounds anandamide (AEA) and 2\u2010arachidonoylglycerol (2\u2010AG) are CB agonists, and, alongside enzymes, they constitute the endocannabinoid system (ECS) and take part in neuromodulation. Several LC\u2010MS\/MS methods have been developed to quantify these compounds in biological matrixes, but a fast and simple method that can determine these analytes in plasma samples simultaneously is not available. Here, we propose a disposable pipette extraction technique containing a zirconia\u2010based sorbent (DPX(Zr)) combined with UHPLC\u2010MS\/MS analysis to determine CBD, THC, AEA, and 2\u2010AG in plasma samples, simultaneously. The method combines simple protein precipitation (PPT) with a one\u2010step DPX procedure to remove phospholipids, one of the most common endogenous interferents in biological samples. Optimization of the combined PPT\u2010DPX sample preparation method reduced the matrix effect and improved the sensitivity of the analytical method. The validated DPX(Zr)\u2010UHPLC\u2010MS\/MS method reported LLOQs of 0.1\u00a0ng mL<jats:sup>\u22121<\/jats:sup> for AEA and 2\u2010AG and 1\u00a0ng mL<jats:sup>\u22121<\/jats:sup> for CBD and THC. The method demonstrated intra\u2010 and interassay accuracy and precision of less than 20% for the LLOQ, and less than 15% for the other calibration points. Additionally, no carryover or significant matrix effect was observed. We applied this method to determine AEA, 2\u2010AG, and CBD in plasma samples obtained from obsessive\u2010compulsive disorder patients treated with CBD.<\/jats:p>","DOI":"10.1002\/jssc.70068","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:56:12Z","timestamp":1736816172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Disposable Pipette Extraction\u2010UHPLC\u2010MS\/MS Method Based on Removal of Phospholipids to Determine Anandamide, 2\u2010Arachidonoylglycerol, Cannabidiol, and \u0394<sup>9<\/sup>\u2010Tetrahydrocannabidiol in Plasma Samples"],"prefix":"10.1002","volume":"48","author":[{"given":"Igor Gustavo Carvalho","family":"Oliveira","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeir\u00e3o Preto University of S\u00e3o Paulo  S\u00e3o Paulo Ribeir\u00e3o Preto\u2010SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel Donizeti","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeir\u00e3o Preto University of S\u00e3o Paulo  S\u00e3o Paulo Ribeir\u00e3o Preto\u2010SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Alexandre de Souza","family":"de Crippa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Behavior Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Ribeir\u00e3o Preto\u2010SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-1884","authenticated-orcid":false,"given":"Maria Eug\u00eania Costa","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeir\u00e3o Preto University of S\u00e3o Paulo  S\u00e3o Paulo Ribeir\u00e3o Preto\u2010SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-3084(00)00184-5"},{"key":"e_1_2_9_3_1","first-page":"19","article-title":"Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor","volume":"1558","author":"Devane W. 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