{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:40:16Z","timestamp":1778550016690,"version":"3.51.4"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background: l-Threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa) is a norepinephrine (NE) prodrug under development to treat orthostatic hypotension. 3,4-Dihydroxyphenylacetaldehyde (DOPAL), an endogenous catecholaldehyde produced by enzymatic oxidative deamination of dopamine, is toxic to catecholaminergic neurons. Based on the observation of increasing plasma DOPAL after oral administration of L-DOPS to a patient, we examined whether other subjects also had DOPAL in their plasma after droxidopa administration, and whether droxidopa is contaminated with DOPAL.<\/jats:p><jats:p>Methods: Thirteen subjects took 400 mg droxidopa orally. We sampled venous blood at baseline and 1, 2, 3, 6, 24, and 48 h after drug administration and assayed L-DOPS, NE, and DOPAL by use of liquid chromatography with electrochemical detection (LC-ED). Droxidopa in acidic solution (20:80 mixture of 0.04 mol\/L phosphoric acid:0.20 mol\/L acetic acid) was vacuum centrifuged for 1 h at 30 \u00b0C and then assayed by LC-ED.<\/jats:p><jats:p>Results: Droxidopa contained 0.01% DOPAL. At 6 h after droxidopa, all subjects had detectable DOPAL in plasma (1.89 nmol\/L, P = 0.0001). Across the sampling times, plasma DOPAL correlated with plasma L-DOPS (r = 0.996). The mean increment in plasma DOPAL was more than 4 times that in plasma NE (0.39 nmol\/L). In 2 patients with Parkinson disease and orthostatic hypotension, DOPAL was detected in plasma at baseline (0.12 nmol\/L) and increased by about 70-fold after droxidopa. Vacuum concentration of droxidopa in the acid solution converted L-DOPS to DOPAL completely.<\/jats:p><jats:p>Conclusions: Droxidopa is contaminated with DOPAL. After oral droxidopa administration, DOPAL is detected in plasma of humans. Droxidopa is susceptible to extensive nonenzymatic conversion to DOPAL.<\/jats:p>","DOI":"10.1373\/clinchem.2009.139709","type":"journal-article","created":{"date-parts":[[2010,3,6]],"date-time":"2010-03-06T02:21:37Z","timestamp":1267842097000},"page":"832-838","source":"Crossref","is-referenced-by-count":10,"title":["Contamination of the Norepinephrine Prodrug Droxidopa by Dihydroxyphenylacetaldehyde"],"prefix":"10.1093","volume":"56","author":[{"given":"Courtney","family":"Holmes","sequence":"first","affiliation":[{"name":"Clinical Neurocardiology Section, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel","family":"Whittaker","sequence":"first","affiliation":[{"name":"Laboratory of Bio-Organic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 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