Bioanalytical method development and validation using incurred samples—Simultaneous quantitation of ramipril and ramiprilat in human EDTA plasma by LC–MS/MS

Tan, Aimin; Jin, Wen; Deng, Fang; Hussain, Saleh; Musuku, Adrien; Massé, Robert

doi:10.1016/j.jchromb.2009.09.017

Cited by 36 publications

(23 citation statements)

References 9 publications

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“…To my knowledge, few studies [13,14] have considered ISS in the presence of AG. Studies of ISS under general situation (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Because maximum plasma concentration (Cmax) was important for the planned toxicity studies, samples around Cmax were used for determining ISS. In contrast to the present study, Tan et al used nine individual samples for frozen long-term stability, 15 individual samples for short-term stability, and three pooled samples for short-term stability, autosampler stability, and freeze-thaw stability [13]. Nouman et al used one pooled sample that was prepared by pooling samples from a subject at multiple sampling time points [14].…”

Section: Issmentioning

confidence: 90%

“…Given that GBC [5], the 7th WRIB [10], and 7th GCC [6] recommended evaluating ISS when metabolites are likely to affect assay results, it is important to discuss the test items and study design of ISS experiments in the presence of AG. Unfortunately, to my knowledge, ISS in the presence of AG has been addressed by only two case studies [13,14]. Further, both test items and the design of the two studies were inconclusive.…”

Section: Introductionmentioning

confidence: 95%

“…Because the test items in the present study included stability during sample collection and extraction, the reference value was acquired from samples for which the times required for sample collection and extraction were minimized as much as possible. This experimental procedure was not employed in studies by either Tan et al [13] or Nouman et al [14], possibly because human incurred samples were used, and because it is generally difficult in a clinical setting to start an analysis immediately after blood collection. Sample H (positive control) helped qualify the use of Sample A as a reference value, because the ASP3258 concentration of Sample H was higher than that of Sample A, suggesting that ASP3258-AG was not completely converted to ASP3258 in Sample A.…”

Section: Issmentioning

confidence: 99%

“…Because an acceptable number of samples for ISS tests can vary for practical reasons, it is advisable to determine the number on a case-by-case basis. Tan et al and Nouman et al chose samples to cover multiple sampling time points [13,14], likely because they planned to use their methods to evaluate full pharmacokinetic profiles. When both Cmax and elimination phase are important in a pharmacokinetic study, it is reasonable to select samples accordingly, because the abundance of AG relative to the analyte can vary depending on the sampling times and the ISS results therefore can change as well.…”

Section: Issmentioning

confidence: 99%

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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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“…To my knowledge, few studies [13,14] have considered ISS in the presence of AG. Studies of ISS under general situation (i.e.…”

Section: Discussionmentioning

confidence: 99%

Section: Issmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 95%

Section: Issmentioning

confidence: 99%

Section: Issmentioning

confidence: 99%

See 3 more Smart Citations

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

Ohtsu¹

2017

J Appl Bioanal

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Development and validation of UPLC tandem mass spectrometry assay for separation of a phase II metabolite of ramipril using actual study samples and its application to a bioequivalence study

Pudage

Kamat

2010

Biomedical Chromatography

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In this paper, we present a validated UPLC-MS/MS assay for determination of ramipril and ramiprilat from human plasma samples. The assay is capable of isolating phase II metabolites (acylglucornides) of ramipril from in vivo study samples which is otherwise not possible using conventional HPLC conditions. Both analytes were extracted from human plasma using solid-phase extraction technique. Chromatographic separation of analytes and their respective internal standards was carried out using an Acquity UPLC BEH C(18) (2.1 × 100 mm), 1.7 µm column followed by mass spectrometric detection using an Waters Quattro Premier XE. The method was validated over the range 0.35-70.0 ng/mL for ramipril and 1.0-40.0 ng/mL for ramiprilat.

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Strategies in quantitative LC‐MS/MS analysis of unstable small molecules in biological matrices

Li¹,

Zhang²,

Tse³

2010

Biomedical Chromatography

125

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Stability is an important pre-analytical variable for quantitative LC-MS/MS analysis of drug molecules and/or their metabolites in biological matrices. Instability of an analyte in any stage of the bioanalytical process, including sample collection, processing, storage, extraction and LC-MS/MS analysis, can result in under-/over-estimation if an adequate preventive procedure is not in place. In the current review on practical strategies in quantitative LC-MS/MS bioanalysis of unstable small molecules, the common causes of analyte instability were examined. The instability of some analytes is readily predictable because of the presence of certain chemically or biologically labile moieties in the molecules or because the compounds are in an inter-convertible form, e.g. lactone vs hydroxyl carboxylic acid. However, the instability of many other analytes is not readily predictable. Necessary evaluation needs to be conducted to identify the possible instability issues. The current review highlighted some general considerations and specific approaches for developing a robust LC-MS/MS method. In particular, incurred samples should be used as part of routine short-term stability assessment of any unstable analyte during the early stages of method development and validation. This can help unveil any 'hidden' instability issues that, if left unaddressed, could lead to the invalidation of a 'validated' method.

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Bioanalytical method development and validation using incurred samples—Simultaneous quantitation of ramipril and ramiprilat in human EDTA plasma by LC–MS/MS

Cited by 36 publications

References 9 publications

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

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

Development and validation of UPLC tandem mass spectrometry assay for separation of a phase II metabolite of ramipril using actual study samples and its application to a bioequivalence study

Strategies in quantitative LC‐MS/MS analysis of unstable small molecules in biological matrices

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