{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T15:21:54Z","timestamp":1792336914774,"version":"4.4.0"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development, AMED","award":["22ek0109511h0002"],"award-info":[{"award-number":["22ek0109511h0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and an essential mediator of energy metabolism. The redox balance between NAD+ and NADH affects various diseases, cell differentiation, and aging, and in recent years there has been a growing need for measurement techniques with improved accuracy. However, NAD(H) measurements, representing both NAD+ and NADH, have been limited by the compound\u2019s properties. We achieved highly sensitive simultaneous measurement of NAD+ and NADH under non-ion pairing, mobile phase conditions of water, or methanol containing 5 mM ammonium acetate. These were achieved using a simple pre-treatment and 7-min analysis time. Use of the stable isotope 13C5-NAD+ as an internal standard enabled validation close to BMV criteria and demonstrated the robustness of NAD(H) determination. Measurements using this method showed that brain NAD(H) levels correlate strongly with plasma NAD(H) levels in the same mouse, indicating that NAD(H) concentrations in brain tissue are reflected in plasma. As NAD(H) is involved in various neurodegenerative diseases and cerebral ischemia, as well as brain diseases such as mitochondrial myopathies, monitoring changes in NADH levels in plasma after drug administration will be useful for development of future diagnostics and therapeutics.<\/jats:p>","DOI":"10.3390\/ijms25042325","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T11:19:01Z","timestamp":1707995941000},"page":"2325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Simple, Fast, Sensitive LC-MS\/MS Method to Quantify NAD(H) in Biological Samples: Plasma NAD(H) Measurement to Monitor Brain Pathophysiology"],"prefix":"10.3390","volume":"25","author":[{"given":"Tamaki","family":"Ishima","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuka","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Osaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Japan"},{"name":"Clinical Pharmacology Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"},{"name":"Division of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tcb.2014.04.002","article-title":"NAD+ and sirtuins in aging and disease","volume":"24","author":"Imai","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.pathol.4.110807.092250","article-title":"Mammalian sirtuins: Biological insights and disease relevance","volume":"5","author":"Haigis","year":"2010","journal-title":"Annu. 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