Determination of cyclic butylboronate esters of some 1,2- and 2,3-diols in plasma by high-resolution gas chromatography/mass spectrometry

Abstract

A gas chromatographic/mass spectrometric analytical procedure is described to determine glycols in plasma as cyclic butyl boronate esters. The method, involving a pre-deproteinization step, required only 0.25 ml of plasma and a short time (20 min) to react with the derivatizing agent (butyl boronic acid). The gas chromatographic separation on a CP Sil 8 CB silica capillary column coupled to a mass detector assured a complete identification of the compounds. The analytical recoveries (greater than 95%) with low coefficient of variation (4-11%) assured the feasibility of the method over a concentration range from 5 to 1000 micrograms ml-1 for each glycol. The lower detection limits, namely 1-5 micrograms ml-1, confirmed the sensitivity of the method.

Sequential Metabolism and Bioactivation of the Hepatotoxin Benzbromarone: Formation of Glutathione Adducts From a Catechol Intermediate

“…However, on the basis of the foregoing structural analysis of metabolite 2 and the similarities between the daughter ion spectra shown in Figures 5A and 5B, metabolite 1 must be either 6,7-or 4,6-dihydroxy-BBR. Further attempts to discriminate between these two possibilities involved GC-MS analysis of cyclic boronate esters (33), whose formation would be indicative of a catechol metabolite. Although 3,4-dihydroxycinnamic acid yielded the expected cyclic boronate, neither metabolite 1 nor 2 was successfully derivatized, suggesting that their higher molecular weights may have hindered volatilization of the compounds.…”

Discovery Tactics To Mitigate Toxicity Risks Due to Reactive Metabolite Formation with 2-(2-Hydroxyaryl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one Derivatives, Potent Calcium-Sensing Receptor Antagonists and Clinical Candidate(s) for the Treatment of Osteoporosis

“…The presence of fragment ions at m / z 324, 304, and 276 in the CID spectra of M5 and M6 (addition of 16 Da to the fragment ions at m / z 308, 288, and 260 in the CID spectrum of 1 ) ruled out the 1-phenylpropan-2-yl substituent as a site of monohydroxylation. To examine whether M6, the major metabolite of 1 , is a catechol derivative, M6 was biosynthesized in HLM, isolated, purified, and reacted with butyl boronic acid, a reagent used to selectively derivatize vicinal diols and catechols , . An aliquot of the crude reaction mixture was mixed with the HPLC mobile phase and directly infused on the mass spectrometer to obtain spectral information for the putative butylboronate derivative.…”

“…To assess whether M6 was a catechol derivative, a solution of purified M6 (∼1 mg) in acetonitrile (5 mL) was treated with butylboronic acid (1 mL of a 25 mg/mL suspension in acetonitrile). After the reaction was stirred for 15 min at 37 °C, an aliquot (0.5 mL) was mixed with mobile phase and directly infused on a Finnigan LTQ spectrometer as well as on the Thermo Orbitrap to obtain MS 2 / MS 3 and full scan accurate mass spectra of M6 and its butylboronate derivative (16).…”

A Prospective Evaluation of Propylene Glycol Clearance and Accumulation During Continuous-Infusion Lorazepam in Critically Ill Patients

“…Plasma PG concentrations were determined using a previously described method. 25 Samples were deproteinized by combining 225 μL of the plasma samples with 500 μL acetic acid:acetone solution (20 μL acetic acid glacial 100% in 10 mL of acetone) and 25 μL internal standard D6-propylene glycol (1:1000; D6-PG), mixing by vortex for 10 seconds and then centrifuging at 4000 rpm for 5 minutes. The supernatant was then added to 250 μL of a butaneboronic acid (BBA) solution (prepared by dissolving 20 mg BBA in 2 mL dimethoxypropane and 12 μL 6 M HCl) and incubated at room temperature for 20 minutes.…”