Despite the existence of good clinical practice guidelines, the way in which they are applied to the bioanalytical laboratory remains unclear. Aspects of patient confidentiality, informed consent and subject withdrawal; addressing unblinding associated with sample analysis, including repeat analysis and incurred sample reanalysis; or the differences in responsibilities between the sponsor and contract research organization are not articulated by the US FDA within the bioanalytical setting, and for most bioanalytical laboratories this remains a gap in their standard operating procedures. The aim of this article is to identify and clarify the aspects of the good clinical practices that are applicable to the bioanalytical laboratory when conducting bioanalysis with clinical samples, and to address potential gaps in the bioanalytical laboratory when it comes to clinical sample bioanalysis.

The use of multiple signature peptides for the quantification of proteins by digestion and LC-MS/MS is reviewed and evaluated here. A distinction is made based on the purpose of the use of multiple peptides: confirmation of the protein concentration, discrimination between different protein forms or species and in vivo biotransformation. Most reports that describe methods with at least two peptides use these for confirmation, but it is not always mentioned how the peptides are used and how possible differences in concentration between the peptides are handled. Differences in concentration are often reported in the case of monitoring different protein forms or in vivo biotransformation, and this offers insight into the biological fate of the protein.

Background: The increasing prevalence of poisoning cases related to antidepressants and antipsychotics has raised concerns. Methods: To address this issue, a new adaptation of the dried plasma spot technique was developed using a 24-well plate and fast gas chromatography-mass spectrometry. The method involves the optimization of extraction variables and sample preparation, and was successfully validated. Results: The limits of quantitation ranged from 20 to 60ng/ml, and accuracy ranged from 87.8% to 112.2%. The technique was applied to 102 human plasma samples from suspected poisoning cases, with positivity of 90.2%. Conclusion: This method provides a cheap, easy to implement and fast approach, making it ideal for toxicological emergency laboratories and promoting valuable support for healthcare professionals managing poisoning cases involving antidepressants and antipsychotics.

Nous proposons un modele generique d'hyperbase destine a integrer des documents structures representes conformement a la norme sgml et/ou semi-structures de type html. Le modele permet egalement de tenir compte des specificites de la composante audio faisant partie de l'hypermedia sonore (ou hyperbase sonore). Un mecanisme semi-automatique qualifie d'hyperisation a ete formalise et developpe pour integrer ces documents dans l'hyperbase. Ce mecanisme repose sur : - l'analyse de la structure des documents, si celle-ci a ete specifiee (via une dtd par exemple) par une structure generique ou si elle peut etre elicitee, decouverte a partir du contenu de l'instance, - leur decomposition en unites structurelles selon un niveau de granularite dependant du contexte, de l'application, - leur stockage dans l'hyperbase conformement au modele de donnees specifie. Le caractere semi-structure de certaines informations et l'heterogeneite des formats et des types imposent un traitement prealable pour les convertir en format neutre exploitable pour leur decomposition. Nous faisons appel pour cela a un outil de reecriture appele exrep dont le principe consiste a reconnaitre des motifs dans le texte du document et a les reecrire conformement a une regle donnee. Cette approche a ete elargie a la problematique d'integration de la composante sonore. Les specificites a prendre en compte pour un tel systeme ont ete etablies, en particulier au niveau de l'unite d'information sonore. L'unite d'information sonore a ete tout d'abord etudiee seule ensuite associee aux autres unites considerees (texte et image). Un modele de consultation sonore a ete propose, puis valide dans le cadre du projet hyperaudio, qui concerne la specification d'une architecture d'hypermedia integrant la composante sonore.

Background: Workplace drug testing primarily relies on urine analysis, targeting multiple compounds with varying physicochemical characteristics. Biocompatible solid-phase microextraction (BioSPME) is a miniaturized solid-phase extraction technique that enables the simultaneous extraction and preconcentration of analytes directly from the biological matrix. Methods: The BioSPME procedure consisted of the sequential extraction of 50-μl urine samples using LC Tips C18 in basic and acidic pH, followed by desorption with methanol and n-hexane, respectively. The extracts were analyzed by ultra-performance LC-MS/MS. Results: Intra-day precision was 1.2-8.6% and inter-day precision was 1.8-14.2%. Accuracy was 96.8-107.4%. The extraction yields were 62.8-109.4%. The matrix effects were -3.98% to 1%. Conclusion: BioSPME shows promise as an alternative method for preparing urine samples prior to drug measurement by ultra-performance LC-MS/MS.

Aim: To describe the stability of nafamostat in infusion solutions, during blood sample collectionand in extracted plasma samples in the autosampler. Methods: Nafamostat infusion solutions were stored at room temperature in the light for 24h. For sample collection stability, fresh blood spiked with nafamostat was subjected to combinations of anticoagulants, added esterase inhibitor and temperature. Nafamostat was monitored in the extracted plasma samples in the autosampler. Results: Nafamostat was stable in infusion solutions. Nafamostat in whole blood was stable for 3h before centrifugation when collected in sodium fluoride/potassium oxalate tubes (4°C). Nafamostat in extracted plasma samples degraded at 4.7±0.7% per h. Conclusion: Viable samples can be obtained using blood collection tubes with sodium fluoride, chilling and processing promptly.

Background: Sodium oligomannate was approved for marketing by the National Medical Products Administration of China in 2019 for improving cognitive functions in mild-to-moderate Alzheimer's disease patients. Method: LC-MS/MS methods were established and validated for the quantitation of sodium oligomannate in human plasma, urine and feces to support clinical development studies. Samples were prepared using liquid-liquid extraction and analyzed by ion-pair reversed-phase LC-MS/MS with calibration standard curve ranges of 25.0-5000ng/ml, 0.500-100μg/ml and 100-10,000μg/g in plasma, urine and feces, respectively. Results & conclusion: All validation parameters met the respective acceptance criteria established by US FDA and International Council for Harmonisation of Technical Requirements for Human Use guidelines. The validated methods were applied to a pharmacokinetics and excretion study in healthy Chinese subjects.

BioanalysisAhead of Print EditorialChronopharmacokinetics: a critical missing step in drug discovery and developmentSiva Nageswara Rao Gajula, Chandraiah Godugu & Rajesh SontiSiva Nageswara Rao Gajula https://orcid.org/0000-0003-0449-4282Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Balanagar, Telangana, 500037, IndiaSearch for more papers by this author, Chandraiah Godugu https://orcid.org/0000-0001-5904-3134Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Balanagar, Telangana, 500037, IndiaSearch for more papers by this author & Rajesh Sonti *Author for correspondence: Tel.: +91 917 727 3849; E-mail Address: rajesh.sonti@niperhyd.ac.inhttps://orcid.org/0000-0001-7631-5605Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Balanagar, Telangana, 500037, IndiaSearch for more papers by this authorPublished Online:31 May 2023https://doi.org/10.4155/bio-2023-0080AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: chronopharmaceuticalschronopharmacokineticschronopharmacologydrug metabolism and pharmacokinetics (DMPK)personalized medicinezeitgebers

Background: Aimed to simultaneously measure linezolid, voriconazole, cefoperazone and fluconazole in human plasma suitable for therapeutic drug monitoring applications, a robust, rapid and easy-to-use HPLC-MS/MS approach was developed and validated. Materials & methods: Protein precipitation was used to prepare analytes from 100μl plasma. HPLC was employed for analyte separation, and quantification was conducted via multiple reaction monitoring in positive ion mode. The methodology was fully validated. Results & conclusion: All four antibiotics were found to be stable under the tested conditions, andaccuracy values rangedfrom 90.96 to 113.25% and CV values were <14.0%. This HPLC-MS/MS method can be used for routine clinical therapeutic drug monitoring of linezolid, voriconazole, cefoperazone and fluconazole simultaneously.

BioanalysisVol. 15, No. 3 ForewordIntroducing the 2023 Bioanalysis special-themed issue on laboratory structure and management for nonregulated bioanalysisQin C Ji & Gary J JenkinsQin C Ji*Author for correspondence: E-mail Address: qin.ji@abbvie.comAbbVie, 1 North Waukegan Road, North Chicago, IL 60064, USASearch for more papers by this author & Gary J Jenkins**Author for correspondence: E-mail Address: gary.jenkins@abbvie.comAbbVie, 1 North Waukegan Road, North Chicago, IL 60064, USASearch for more papers by this authorPublished Online:30 Mar 2023https://doi.org/10.4155/bio-2023-0037AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View article