High-Performance Liquid Chromatography Assay for Moxifloxacin in Brain Tissue and Plasma: Validation in a Pharmacokinetic Study in a Murine Model of Cerebral Listeriosis

Abstract

<jats:p>Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mn>250</mml:mn><mml:mo>×</mml:mo><mml:mn>4.6</mml:mn></mml:math> mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mtext>pH</mml:mtext><mml:mo>=</mml:mo><mml:mn>3.5</mml:mn></mml:math>) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290 nm and an emission wavelength of 550 nm. The relative standard deviation of intra- and inter-day assays was &lt;10%. This validated method led to a short retention time (8.0 min) for moxifloxacin. The standard curves were linear from 5–250 <jats:italic>μ</jats:italic>g/L in plasma and from 0.1–2.5 <jats:italic>μ</jats:italic>g/g of brain tissue. The limits of quantification were 5 <jats:italic>μ</jats:italic>g/L in plasma and 0.1 <jats:italic>μ</jats:italic>g/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS in<jats:italic>Listeria</jats:italic>-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice.</jats:p>

Assessment of brain‐to‐blood drug distribution using liquid chromatography

“…administration ESI, electrospray ionization; i.n., intranasal; LLE, Liquid-liquid extraction; LLOQ, lower limit of quantitation; LOD, limit of detection; LOQ, limit of quantitation; NA, not applicable; TEA, triethylamine. Colovic & Caccia, 2003;Colovic et al, 2004;Dalvi et al, 2018;Gaudreault et al, 1996;Guo et al, 2007;Haque et al, 2012;Labuzek et al, 2010;Liang et al, 1999;Liang et al, 2012;Nirogi et al, 2013;Respaud et al, 2012;Saigusa et al, 2011;Shimokawa et al, 2005;Singh et al, 2011;Su et al, 2015;Sweeney et al, 1985;Teoh et al, 2010;Weigmann et al, 1999;Workman et al, 1984;Zheng et al, 2015;Zhou & Gallo, 2010). Organic acid additives including formic acid in aripiprazole extraction (Liang et al, 2012), acetic acid in imatinib and sunitinib extractions (Teoh et al, 2010;Zhou & Gallo, 2010) and citric acid for treosulfan and its metabolie monoepoxy transformer (S,S-EBDM) extractions (Roma nski et al, 2014) were added to organic precipitants to effectively reduce protein binding.…”

“…The most common methods utilize C 18 reversed phase (RP) columns with varying ratios of mobile phases, as shown in Table 1. The columns used are: Waters Atlantis (El Yang et al, 2015;Zhang et al, 2007bZhang et al, , 2007c, Ultrasphere (Shibanoki et al, 1984), Agilent Eclipse Plus (Liang et al, 2012), Hypersil (Couet et al, 1990;Jiang et al, 2008;Nicot et al, 1986;Weigmann et al, 1999), μBondpack (Colovic et al, 2004;Lister et al, 1983;Somani & Khalique, 1985), Phenomenex Kinetex (Dalvi et al, 2018), Develosil (Nakashima et al, 2002;Nakashima et al, 2003), Xbridge (Nirogi et al, 2013), XTerra ® MS (Ligneau et al, 2007;Minocha et al, 2012), Cosomil (Yasir et al, 2017), LiChrospher (Castel-Branco et al, 2003Respaud et al, 2012), Intersil ODS-2 (Ohmori et al, 2000), Wakopak Handy ODS (Tomita et al, 2007), LiChroCART (Fortuna et al, 2013;Haque et al, 2012;Singh et al, 2011), Zorbax Eclipse (Oberoi et al, 2013;Roma nski et al, 2014;Wang et al, 2011), Gemini (Perin et al, 2017;Zheng et al, 2015), Radial-PAK (Workman et al, 1984), Partosil 10 (Greig et al, 1988Sweeney et al, 1985), Luna (Guo et al, 2007;Saigusa et al, 2011), Agilent SB …”

“…These lead to exceptional sensitivity, specificity and dynamic range, which are necessary for the effective detection of these drugs in both matrices and the accurate determination of the brain-to-blood ratio (Al-Ghananeem et al, 2010;Ayoub et al, 2018;Chang et al, 2015;El Zahar et al, 2018;Guo et al, 2007;Li et al, 2012;Li et al, 2013;Liang et al, 2012;Ligneau et al, 2007;Md et al, 2014;Minocha et al, 2012;Nirogi et al, 2013;Oberoi et al, 2013;Ohmori et al, 2000;Roma nski et al, 2014;Su et al, 2015;Turnpenny & Fraier, 2009;Wang et al, 2011;Xia et al, 2004;Yang et al, 2015;Zhang et al, 2007bZhang et al, , 2007cZhang et al, , 2008Zheng et al, 2015;Zhou & Gallo, 2010). Fluorescence detection has been performed for the detection of appropriate molecules as in the case of donepezil and moxifloxacin (Nakashima et al, 2006;Respaud et al, 2012). Other fluorometric assays allow for the analysis of melphalan after its derivatization with o-phthalaldehyde (Sweeney et al, 1985), the determination of MDMA with its metabolite MDA and the determination of a mixture of phentermine, fenfluramine and its metabolite norfenfluramine after being subjected to derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (Kaddoumi et al, 2003;Tomita et al, 2007).…”

Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model

“…Determination of MXF Blood Levels by LC-MS. MXF blood concentrations were determined by a modification of published methods. 40,41 Heparinized blood (0.1 mL) was collected by retro-orbital bleed at sequential times after administration of free MXF or MSN-SS-MXF i.v. or i.m.…”

A Stability-Indicating High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Pyridoxine, Ethionamide, and Moxifloxacin in Fixed Dose Combination Tablets

“…The later concentration is found to be successful in reducing the tailing effect. Finally to make the method cost effective, acetonitrile was replaced by methanol; this intervention further improved the resolution between the peaks of ETH and MOX with a provision of adding ciprofloxacin as internal standard [28].…”