Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method

Foivas, Anargyros; Malenović, Anđelija; Kostić, Nikola; Božić, Marija; Knežević, Miloš; Loukas, Yannis L.; Dotsikas, Yannis

doi:10.1016/j.jpba.2015.11.043

Cited by 13 publications

(5 citation statements)

References 10 publications

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“…The computation work is based on the principle of correction through the use of specific, linear-type mathematical formulas correlating a dependent variable of blood spreading with the measured Ht. The current work was performed with the utilization of the mathematical Formula (1), as derived and described in our laboratory’s previous research [ 27 , 56 ]. The computational approach included a simple modeling component as well as Monte Carlo simulations with the creation of virtual neonate populations with different Ht levels that was implemented.…”

Section: Methodsmentioning

confidence: 99%

Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect

et al. 2023

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Dried blood spot (DBS) microsampling is extensively employed in newborn screening (NBS) and neonatal studies. However, the impact of variable neonatal hematocrit (Ht) values on the results can be a source of analytical error, and the use of fixed Ht for calibration (Htcal) is not representative of all neonatal subpopulations. A computational approach based on neonatal demographics was developed and implemented in R® language to propose a strategy using correction factors to address the Ht effect in neonatal DBS partial-spot assays. A rational “tolerance level” was proposed for the Ht effect contribution to the total analytical error and a safe Ht range for neonatal samples, where the correction of concentrations can be omitted. Furthermore, an “alert zone” for a false positive or negative result in NBS was proposed, where the Ht effect has to be considered. Results point toward the use of Htcal values closely representative of populations under analysis and an acceptable level of percentage relative error can be attributed to the Ht effect, diminishing the probability of correction. Overall, the impact of the Ht effect on neonatal studies is important and future work may further investigate this parameter, correlated to other clinical variables potentially affecting results.

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Section: Methodsmentioning

confidence: 99%

Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect

et al. 2023

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“…The obtained results may be used for determination of the time intervals of excreta collection in the elimination study, correction of time points of organ and tissue collection in the distribution study, as well as calculation of the analytical range of bioanalytical methods for quantification of the analytes in these biological objects. Previously developed drugs of the group iCAII such as dorzolamide (Lo Faro et al 2021;Kintz et al 2022) and brinzolamide (Foivas et al 2016;Madrewar et al 2022) are able to accumulate in red blood cells. Therefore, additional calculation of pharmacokinetic parameters of OXSA and OXSA-M1 in blood is necessary for full evaluation of systemic exposure of the substances.…”

Section: Introductionmentioning

confidence: 99%

Development of quantification methods of a new selective carbonic anhydrase II inhibitor in plasma and blood and study of the pharmacokinetics of its ophthalmic suspension in rats

Khokhlov,

Yaichkov,

Korsakov

et al. 2023

RRP

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Introduction: Development of new bioanalytical methods is required for studying the systemic exposure of new selective inhibitor of carbonic anhydrase II, 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide, and its N-hydroxymetabolite in plasma and in whole blood. The results of the experiment with a single administration of an ophthalmic suspension of the drug are necessary to optimize the subsequent design of a full pharmacokinetic study. Materials and Methods: HPLC-MS/MS method was used to measure a concentration of analytes in plasma and whole blood. Chromatographic separation was performed on the Poroshell 120EC-C18 column (50*3.0 mm, 2.7 µm). Pharmacokinetics was studied on 6 Wistar rats weighing 287.50±18.64 g (Mean±SD). Each animal was instilled with 40 µL of the ophthalmic suspension in concentration of 2% in each eye. Blood samples were collected before administration of the drug and 30 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, and 72 h after administration. Non-compartment approach was used for the evaluation of pharmacokinetic parameters. Results and Discussion: The protein precipitation was chosen for a sample preparation of biological fluids. A solution of ascorbic acid in concentration of 10% was added to plasma, and a solution of sodium thiosulfate in concentration of 10% was added to blood to prevent the degradation of N-hydroxymetabolite of the drug. The analytical range of determination of 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide and its N-hydroxyderivative in blood was 50-10000 ng/mL and 5-1000 ng/mL, respectively, in plasma – 10-2000 ng/mL and 1-200 ng/mL, respectively. The maximum plasma concentration of the studied drug was 264.32±68.47 ng/mL (Mean±SD) 1.92±0.92 h (Mean±SD) after administration, and its metabolite was 10.43±1.79 ng/mL 2.17±1.13 h after administration. The maximum concentration of the drug in blood reached 8705.23±1301.84 ng/mL (Mean±SD) 1.17±0.52 h (Mean±SD) after administration, and the maximum concentration of N-hydroxymetabolite reached 230.00±69.54 ng/mL (Mean±SD) 1.33±0.41 h (Mean± SD) after administration. Conclusion: The developed methods have been fully validated according to the requirements of Russian and internatonal guidelines and have been successfully used for pharmacokinetic research. It was found that a content of 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide and its main metabolite in whole blood is significantly higher than in plasma.

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“…Presently, only few analytical methods 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 for the detection of CAIs in biological samples have been published in the international literature and none of them simultaneously determined the three main CAIs (dorzolamide, brinzolamide, and acetazolamide) and/or their metabolites.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, the identification of CAIs in urine and other biological matrices to provide orthogonal data on exposure (e.g., hair) can be of interest to document misuse. 8 Presently, only few analytical methods [9][10][11][12][13][14][15][16][17][18] for the detection of CAIs in biological samples have been published in the international literature and none of them simultaneously determined the three main CAIs (dorzolamide, brinzolamide, and acetazolamide) and/or their metabolites.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a fast ultra‐high‐performance liquid chromatography tandem mass spectrometry method for determining carbonic anhydrase inhibitors and their metabolites in urine and hair

Faro

Tini

Gottardi³

et al. 2021

Drug Testing and Analysis

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A new, rapid, sensitive, and comprehensive ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for quantifying diuretics (acetazolamide, brinzolamide, dorzolamide, and their metabolites) in human urine and hair was developed and fully validated. Twenty-five milligrams of hair were incubated with 500-μl M3 ® buffer reagent at 100 C for 1 h for complete digestion. After cooling, 1-μl supernatant was injected onto chromatography system. Urine samples were simply diluted before injection. The chromatographic run time was short (8 min) through a column with a mobile phase gradient. The method was linear (determination coefficients always higher than 0.99) from limit of quantification (LOQ) to 500 ng/ml in urine and from LOQ to 10 ng/mg in hair. LOQs ranged from 0.07 to 1.16 ng/ml in urine and from 0.02 to 0.15 ng/mg in hair. No significant ion suppression due to matrix effect was observed, and process efficiency was always higher than 80%. Intra-and inter-assay precision was lower than 15%. The suitability of the methods was tested with six urine and hair specimens from patients treated with acetazolamide, dorzolamide, or brinzolamide for ocular diseases or systemic hypertension. Average urine concentrations were 266.32 ng/ml for dorzolamide and 47.61 ng/ml for N-deethyl-dorzolamide (n = 3), 109.27 ng/ml for brinzolamide and 1.02 ng/ml for O-desmethyl-brinzolamide (n = 2), and finally, 12.63 ng/ml for acetazolamide. Average hair concentrations were 5.94 ng/mg for dorzolamide and 0.048 ng/mg for N-deethyl-dorzolamide (n = 3), 3.26 ng/mg for brinzolamide (n = 2), and 2.3 ng/mg for acetazolamide (n = 1). The developed method was simple and fast both in the extraction procedures making it eligible in high-throughput analysis for clinical forensic and doping purposes.

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Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method

Cited by 13 publications

References 10 publications

Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect

Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect

Development of quantification methods of a new selective carbonic anhydrase II inhibitor in plasma and blood and study of the pharmacokinetics of its ophthalmic suspension in rats

Development and validation of a fast ultra‐high‐performance liquid chromatography tandem mass spectrometry method for determining carbonic anhydrase inhibitors and their metabolites in urine and hair

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