title: Determination of cefadroxil in rat plasma and urine using LC-MS/MS and its application to pharmacokinetic and urinary excretion studies.
abstract: A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of cefadroxil, a first-generation cephalosporin, in rat plasma and urine. Rat samples were deproteinized with methanol, and then injected into the LC-MS/MS system (electro-spray ionization, positive mode) for quantification. Drugs were separated on a Synergi™ 4 μm Polar-RP 80A column (150 mm × 2.0 mm, 4 μm) with a mixture of 0.1% formic acid and methanol (62:38, v/v) as the mobile phase at 0.2 mL/min. Detection was performed using multiple reaction-monitoring modes at m/z 364.1→208.1 (for cefadroxil) and m/z 368.1→174.2 (for cefaclor, the internal standard). Method was specific and linear over the concentration range of 10-10,000 ng/mL. Validation parameters for cefadroxil, including accuracy, precision, absolute matrix effect, and stability in rat plasma and urine, were acceptable according to the biological method validation guidelines of the FDA (2001) [16]. Cefadroxil levels in plasma up to 1440 min or 480 min and urine up to 96 h were quantifiable following oral and intravenous cefadroxil administrations to rats at a dose of 2mg/kg, each, suggesting that the method is appropriate for routine pharmacokinetic studies including urinary recovery in rats.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyo-Eon
authors.initials: HE
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Inje University, Gimhae, Gyeongnam, Republic of Korea.
authors.forename: In-Bong
authors.initials: IB
authors.lastname: Kim
authors.affiliation: C&C Research Laboratories, Suwon, Gyeonggi, Republic of Korea.
authors.forename: Yu Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Inje University, Gimhae, Gyeongnam, Republic of Korea.
authors.forename: Kwan Hyung
authors.initials: KH
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Inje University, Gimhae, Gyeongnam, Republic of Korea. Electronic address: maenghj@inje.ac.kr.
authors.forename: Han-Joo
authors.initials: HJ
authors.lastname: Maeng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D002434:Cefadroxil / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D002434:Cefadroxil
keywords: AUC; AUC(∞); AUMC(∞); C(max); Cefadroxil; ESI; HPLC; LC–MS/MS; LOD; LOQ; MRM; MS/MS; Pharmacokinetics; Plasma; QC; RSD; Rat; SPE; T(max); Urine; area under the first moment–time curve from time zero to infinity; area under the plasma concentration curve; electro-spray ionization; high-performance liquid chromatography; limit of detection; limit of quantification; multiple reaction monitoring; peak plasma concentration; quality control; relative standard deviation; slope of the log-linear portion of the concentration time profile; solid-phase extraction; t(1/2); tandem mass spectrometry; terminal phase half-life; time to reach C(max); total area under the plasma concentration–time curve from time zero to infinity; λ