A new approach to evaluate regression models during validation of bioanalytical assays

Singtoroj, Thida; Tärning, Joel; Annerberg, Anna; Ashton, Michael; Bergqvist, Yngve; White, Nicholas J.; Lindegårdh, Niklas; Day, Nicholas

doi:10.1016/j.jpba.2005.11.006

Cited by 58 publications

(50 citation statements)

References 31 publications

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“…This model of calibration, described by Singtoroj et al (45), was found well suited to best fit the criteria of homoscedasticity (homogeneity of variance over the entire calibration range and minimum bias for each single calibrator) (data not shown). The regression coefficients r 2 of all calibration curves were Ͼ0.99, with back-calculated concentrations of the calibration samples being within Ϯ15% (Ϯ20% at the LLOQs) of the nominal concentrations.…”

Section: Chromatogramsmentioning

confidence: 88%

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Décosterd¹,

Rochat

Pesse

et al. 2010

Antimicrob Agents Chemother

113

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Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method requiring 100 l of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 g/ml; those of echinocandin quantification, 0.06 to 0.1 g/ml), accurate (intra-and interassay biases of ؊9.9 to ؉5% and ؊4.0 to ؉8.8%, respectively), and precise (intra-and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 g/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.Differences in oral drug bioavailability, altered volumes of distribution, drug-drug interactions, impaired hepatic and/or renal drug clearance, and the genetic background of hepatic metabolism contribute to the large intra-and interindividual variability of pharmacokinetics of antifungal agents in patients with life-threatening fungal infections. A given drug dosing regimen can yield very different plasma concentrations: subtherapeutic drug exposure may result in a lack of response to therapy and emergence of fungal resistance, while overexposure may increase the risk of toxicity (21,48,57,59). There is therefore increasing clinical evidence of the usefulness of therapeutic drug monitoring (TDM), which allows real-time adjustment of antifungal dosing aimed at optimizing the individual drug's pharmacokinetic/pharmacodynamic profile. This may be especially helpful for severely ill patients with multiple organ dysfunctions and comedi...

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Section: Chromatogramsmentioning

confidence: 88%

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Décosterd¹,

Rochat

Pesse

et al. 2010

Antimicrob Agents Chemother

113

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“…8,36 As concentrações dos analitos são determinadas por meio de regressões obtidas a partir das curvas de calibração e, embora em alguns casos seja necessária a utilização de calibração não-linear, normalmente se opta pela regressão linear, por sua maior simplicidade e aplicabilidade. 1,37 A elaboração de um modelo de regressão pressupõe a existência de um conjunto de pontos que apresentam uma tendência regular e que podem ser representados por uma função matemática, que normalmente é escolhida através de um processo de ajuste conhecido como método dos mínimos quadrados. Portanto, estabelece-se a tendência da variável dependente (y) em função da variável independente (x) que, para uma regressão linear, pode ser expressa como y = ax + b, onde a é o coeficiente angular da reta e b seu intercepto com o eixo y (ou coeficiente linear).…”

Section: Construção E Avaliação De Modelos De Regressãounclassified

“…Porém, mesmo quando se obtém valores de r próximos a 1 ou -1, é possível que a regressão não seja linear ou que o modelo de regressão linear proposto não atenda a faixa de concentração estabelecida. 37,39 Pode-se verificar se a equação de regressão linear é estatisticamente significativa através dos seguintes testes: ajuste do modelo linear, validade da regressão, eficiência da regressão e eficiência máxima.…”

Section: Construção E Avaliação De Modelos De Regressãounclassified

Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas

Cassiano¹,

Barreiro²,

Martins³

et al. 2009

Quím. Nova

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“…The approach to choosing the best regression model was in accordance with the strategy proposed in the previous paper (Singtoroj et al , 2006). Different regression models with or without data transformations and with different weightings were evaluated using model options in EZchrom Elite version 3.18 HPLC System Manager Software (Merck–Hitachi Japan ).…”

Section: Methodsmentioning

confidence: 99%

An HPLC method with diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from Plasmodium vivax patients in Vietnam, using quinine as an internal standard

Pham

Nguyen

Khanh

et al. 2016

Biomedical Chromatography

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A sensitive, simple method for quantification of chloroquine (CQ) and desethylchloroquine (MCQ) in whole blood and plasma from Plasmodium vivax patients has been developed using HPLC with diode array detection (DAD). Solid‐phase extraction on Isolute‐96‐CBA was employed to process 100 μL of plasma/whole blood samples. CQ, MCQ and quinine were separated using a mobile phase of phosphate buffer 25 mm, pH 2.60–acetonitrile (88:12, v/v) with 2 mm sodium perchlorate on a Zorbax SB‐CN 150 × 4.6 mm, 5 μm column at a flow rate of 1.2 mL/min, at ambient temperature in 10 min, with the DAD wavelength of 343 nm. The method was linear over the range of 10–5000 ng/mL for both CQ and MCQ in plasma and whole blood. The limit of detection was 4 ng/mL and limit of quantification was 10 ng/mL in both plasma and blood for CQ and MCQ. The intra‐, inter‐ and total assay precision were <10% for CQ and MCQ in plasma and whole blood. In plasma, the accuracies varied between 101 and 103%, whereas in whole blood, the accuracies ranged from 97.0 to 102% for CQ and MCQ. The method is an ideal technique with simple facilities and instruments, bringing about good separation in comparison with previous methods. © 2016 The Authors Biomedical Chromatography Published by John Wiley & Sons Ltd

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A new approach to evaluate regression models during validation of bioanalytical assays

Cited by 58 publications

References 31 publications

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas

An HPLC method with diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from Plasmodium vivax patients in Vietnam, using quinine as an internal standard

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