Incurred Sample Reanalysis: Different Evaluation Approaches on Data Obtained for Spironolactone and its Active Metabolite Canrenone

Voicu, Victor; Gheorghe, Mihaela; Sora, Iulia; Sârbu, Costel; Medvedovici, Andrei

doi:10.4155/bio.11.83

Cited by 9 publications

(8 citation statements)

References 27 publications

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“…The authors believe that a thorough investigation of ISR failures is critical to understanding the nature of the errors (what drug types, matrices, and/or assay conditions) and how the errors can be tightly controlled during study sample analysis to provide accurate and reliable results. Various tools to investigate ISR data have been reported in literature (12,16,18), and some of them have been used in this article to understand the in vivo ISR data.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Imprecision in Incurred Sample Reanalysis for Small Molecules

Subramaniam¹,

Patel²,

Davit

et al. 2014

AAPS J

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Abstract. Over the years, incurred sample (IS) reanalysis (ISR) has become a tool to confirm the reliability of bioanalytical measurements. The recommendation for ISR acceptance criterion for small molecules is at least 67% of ISR samples that have reanalyzed concentrations within 20% of their original concentrations when normalized to their means. To understand the relevance of the ISR acceptance criterion and sample size requirements, simulated ISR studies evaluated the probability of ISR studies passing the acceptance criterion (ISR pass rate) as a function of IS imprecision and sample size. When IS imprecision (percent coefficient of variation: %CV) is low (≤10 or 1-10% CV), high ISR pass rate (≥99%) is attained with <50 samples. At intermediate IS imprecision (e.g., 12% CV or 7-12% CV range), 80-160 samples are required for a high ISR pass rate. When IS imprecision is at the higher end of the acceptance limit, ISR pass rate decreases significantly, and increasing sample size fails to achieve high ISR pass rate. The effect of systematic bias (e.g., instability, interconversion) on ISR pass rate is strongly dependent on sample size at intermediate IS imprecision. The results provide an understanding of the effect of IS imprecision on ISR pass rates and a framework for selection of ISR sample sizes.

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Section: Discussionmentioning

confidence: 99%

Analysis of Imprecision in Incurred Sample Reanalysis for Small Molecules

Subramaniam¹,

Patel²,

Davit

et al. 2014

AAPS J

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“…there is no concern associated with AG) appear to assume that an interfering metabolite, if present, is moderately stable, because a typical reference value is established from a sample that is collected without special care, shipped in a frozen state, and measured at a bioanalytical laboratory. A number of case studies typically determined frozen long-term stability [18][19][20][21][22][23][24][25][26], some of which also examined other test items. Test items and study design were surveyed by EBF [27] and GCC [7] and extensively discussed by Yadav et al [28].…”

Section: Discussionmentioning

confidence: 99%

Incurred sample stability of ASP3258 in the presence of its acyl glucuronide

Ohtsu¹

2017

J Appl Bioanal

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The acyl glucuronide (AG) of ASP3258 was abundant in incurred monkey samples, and because an AG generally back-converts to its aglycone, accurate quantification of ASP3258 in monkey plasma was a challenge. To prevent the back-conversion of ASP3258-AG, cooling and acidification were incorporated during sample collection, storage, and extraction. To demonstrate that the AG did not affect the determination of ASP3258, the present study used incurred samples to examine whole blood stability, short-term stability, freeze-thaw stability, frozen stability, and stability during extraction. The concentration changes were within −11.4% to 15.0% compared with a reference value and were therefore judged acceptable. The present study presents a detailed account of test items, a reference value, sample numbers, sample selection, and an equation for assessment in the incurred sample stability tests. This bioanalytical method was applied successfully to a study of the toxicokinetics of ASP3258 in monkeys.Keywords: incurred sample stability, acyl glucuronide, ASP3258, animal plasma, toxicokinetics. IntroductionThe potent phosphodiesterase 4 inhibitor ASP3258 (Figure 1) is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease [1]. We previously developed and validated a bioanalytical method to quantify ASP3258 in rat plasma [2]. Because ASP3258 metabolite was not detected in rat plasma [3], this bioanalytical method was developed without encountering issues associated with the metabolite. Subsequently, monkey toxicity studies were planned that required an appropriate bioanalytical method. When ASP3258 was orally administered to monkeys in a preliminary study, the acyl glucuronide (AG) metabolite of ASP3258 was detected in abundance in monkey plasma (data on file), in contrast to our findings using rat plasma [3]. In general, AGs readily back-convert to aglycones, causing overestimation of

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“…Knowing the metabolism is critical to measuring the correct components by the correct procedures [17,18]. A full understanding of the biotransformation also greatly reduces the risk of metabolite interference or conversion to another analyte [19][20][21]. For a xenobiotic drug candidate, interference is more frequently due to a Phase II conjugate such as an N-or O-glucuronide when in-source fragmentation of a co-eluting conjugate can be hidden under the parent peak.…”

Section: Knowing Your Drug's Metabolismmentioning

confidence: 99%

Making Methods Rugged for Regulated Bioanalysis

et al. 2015

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Methods started in discovery are optimized as they progress through preclinical and clinical development. Making a robust assay includes testing individual steps for consistency and points of failure. Assays may be transferred, optimized and revalidated several times. A rugged assay will not only meet regulatory requirements, but will execute with a low failure rate and confirm results under repeat analysis. Challenging aspects such as differential recovery, sample stabilization, resolution of isomers or conjugate analysis must be tackled and made routine. The proper selection of the IS can overcome limitations. It is best to know the potential points of failure before a study has started, but lessons learned from each study also provide invaluable insights to improve assay ruggedness.

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Incurred Sample Reanalysis: Different Evaluation Approaches on Data Obtained for Spironolactone and its Active Metabolite Canrenone

Cited by 9 publications

References 27 publications

Analysis of Imprecision in Incurred Sample Reanalysis for Small Molecules

Analysis of Imprecision in Incurred Sample Reanalysis for Small Molecules

Incurred sample stability of ASP3258 in the presence of its acyl glucuronide

Making Methods Rugged for Regulated Bioanalysis

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