Papers by Mohammed Nur Jemal
Bioanalysis, 2011
The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Vali... more The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Validation Group as a 2-day full immersion workshop for pharmaceutical companies, CROs and regulatory agencies to discuss, review, share perspectives, provide potential solutions and agree upon a consistent approach to recent issues in the bioanalysis of both small and large molecules. High quality, better compliance to regulations and scientific excellence are the foundation of this workshop. As in the previous editions of this significant event, recommendations were made and a consensus was reached among panelists and attendees, including industry leaders and regulatory experts representing the global bioanalytical community, on many ‘hot’ topics in bioanalysis. This 2011 White Paper is based on the conclusions from this workshop, and aims to provide a practical reference guide on those topics.
Bioanalysis, 2012
Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agenc... more Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agencies participated in the 6th Workshop on Recent Issues in Bioanalysis (WRIB). Like the previous sessions, this event was in the format of a practical, focused, highly interactive and informative workshop aiming for high-quality, improved regulatory compliance and scientific excellence. Numerous ‘hot’ topics in bioanalysis of both small and large molecules were shared and discussed, leading to consensus and recommendations among panelists and attendees representing the bioanalytical community. The major outcome of this year’s workshop was the noticeable alignment of multiple bioanalytical guidance/guidelines from different regulatory agencies. This represents a concrete step forward in the global harmonization of bioanalytical activities. The present 2012 White Paper acts as a practical and useful reference document that provides key information and solutions on several topics and issues i...
JALA: Journal of the Association for Laboratory Automation, 2008
There are several advantages to using liquid-filled automated liquid-handling systems equipped wi... more There are several advantages to using liquid-filled automated liquid-handling systems equipped with reusable fixed tips for sample handling of bioanalytical assays. However, liquid-handling parameters that have not been optimized can lead to sample dilution by the system liquid of the automated liquid handler causing possible inaccuracy of sample delivery. In this investigation, liquid-handling parameters involving sample delivery, such as aspiration speed, dispense speed, partition volume, excess volume, and air gaps, were closely examined to understand their roles in the accurate delivery of the sample. Consequently, two strategies for optimization of the parameters are presented that achieve accurate sample delivery while maintaining sample integrity.
JALA: Journal of the Association for Laboratory Automation, 2006
A significant difference between the reported volumes delivered by a fluid-filled automated liqui... more A significant difference between the reported volumes delivered by a fluid-filled automated liquid-handling system with eight stainless steel fixed tips was observed when a gravimetric method and a dual dye photometric method were used to measure delivered volumes between 20 and 200 μL. A series of experiments, using the default pipetting parameters, was performed which demonstrated that the difference in the reported volume was due to a dilution effect by the system liquid of the liquid handler and did not indicate an error in the delivered volumes. This dilution effect led to a decrease in the reported volume by the dual dye method, which alerted the user to the problem of sample dilution. In contrast, the gravimetric method provided the expected volume, and therefore did not alert the user to the problem. Without optimization of pipetting parameters, the dilution issue can be significant, because the resultant change in the concentration of the compound(s) of interest in the samp...
Bioanalysis, 2010
The 4th Calibration and Validation Group Workshop on Recent Issues in Regulated Bioanalysis, a 2-... more The 4th Calibration and Validation Group Workshop on Recent Issues in Regulated Bioanalysis, a 2-day full immersion workshop, was organized by the Calibration and Validation Group. Contract research organizations, pharmaceutical companies and regulatory agencies came together to discuss several 'hot' topics concerning bioanalytical issues and regulatory challenges and to reach a consensus among panelists and attendees on many points regarding method validation of small and large molecules.
Journal of laboratory automation, 2012
Biological sample dilution is a rate-limiting step in bioanalytical sample preparation when the c... more Biological sample dilution is a rate-limiting step in bioanalytical sample preparation when the concentrations of samples are beyond standard curve ranges, especially when multiple dilution factors are needed in an analytical run. We have developed and validated a Microsoft Excel-based robotic sample preparation program (RSPP) that automatically transforms Watson worklist sample information (identification, sequence and dilution factor) to comma-separated value (CSV) files. The Freedom EVO liquid handler software imports and transforms the CSV files to executable worklists (.gwl files), allowing the robot to perform sample dilutions at variable dilution factors. The dynamic dilution range is 1- to 1000-fold and divided into three dilution steps: 1- to 10-, 11- to 100-, and 101- to 1000-fold. The whole process, including pipetting samples, diluting samples, and adding internal standard(s), is accomplished within 1 h for two racks of samples (96 samples/rack). This platform also suppo...
Drug Metabolism and Disposition, 2012
Biomedical Chromatography, 2010
This treatise summarizes the underlying principle and the road map for systematic LC‐MS/MS bioana... more This treatise summarizes the underlying principle and the road map for systematic LC‐MS/MS bioanalytical method development. The three themes that have recently emerged as central to building quality during method development—phospholipids, incurred sample and sound chromatographic considerations—are the main focus of this article. In order to reduce the bioanalytical risk associated with plasma phospholipids, a dual approach involving extraction and chromatography is recommended. The use of incurred sample during method development is essential to avoid interference arising from drug‐related components. This is different from the current practice of incurred sample reanalysis, which tests reproducibility during method application. LC column/mobile phase optimization is needed to achieve appropriate peak shape, sensitivity and the separation of the analyte from interfering metabolites and phospholipids. Related to sound chromatographic considerations, we lay out facts and myths rela...
Analytical Chemistry, 2009
The understanding and control of the in-source collision-induced dissociation (CID) of analytes i... more The understanding and control of the in-source collision-induced dissociation (CID) of analytes is important for the accurate LC-MS/MS quantitation of drugs and metabolites in biological samples. Accordingly, it was of interest to us to establish whether such in-source CID takes place after and/or before the orifice of an electrospray ionization (ESI) mass spectrometer. A high-field asymmetric waveform ion mobility spectrometry (FAIMS) system that is physically located between the sprayer and the orifice of a mass spectrometer can serve as an ion filter to control ions entering the orifice of the mass spectrometer. In such a configuration, FAIMS could conceivably be used to determine if the in-source CID of an analyte occurs after and/or before the mass spectrometer orifice. We demonstrated this capability of FAIMS using ifetroban acylglucuronide metabolite as a model compound. Under the conditions used, the results showed that the in-source CID conversion of the acylglucuronide metabolite to its parent drug ifetroban occurred almost entirely after the orifice of the mass spectrometer, with the conversion upstream of the orifice accounting for only 5.6% of the conversion. Under the circumstance, the term "post-orifice CID" rather than "in-source CID" may be more appropriate in describing such a dissociation occurring in the front end of a mass spectrometer.
Drug Metabolism and Disposition, 2006
Journal of Chromatography B: Biomedical Sciences and Applications, 1997
As it is extremely unstable in blood, the thiol compound BMS186716 was stabilized by the addition... more As it is extremely unstable in blood, the thiol compound BMS186716 was stabilized by the addition of methyl acrylate (MA) to blood samples. The blood samples were then kept in ice for 10-15 min for completion of the Michael addition reaction to occur between the thiol group of BMS186716 and MA, after which the plasma was separated by centrifugation under refrigeration. For sample analysis, the standard and quality control samples were prepared by spiking blank plasma with the BMS186716-MA adduct. After addition of the internal standard, BMS 188035-MA, each sample was acidified with HCI and then extracted with methyl tert.-butyl ether. Each reconstituted extract was injected into a high-performance liquid chromatography-positive ion electrospray ionization mass spectrometric system. The electrospray condition was chosen to enhance the [M+NH4]+ signal at the expense of the [M+H]+ signal. Monitoring the [M+NH4]+ signal, a lower limit of quantitation of 2.5 ng/ml was achieved, with 0.5 ml plasma. We have thus shown that a sulfhydryl compound (BMS186716) in blood can successfully be stabilized by reacting it with MA and that the adduct produced is adequately stable in blood and plasma to allow the development of a rugged quantitative bioanalytical method.
Journal of Biochemical and Biophysical Methods, 2000
Biological samples are normally collected and stored frozen in capped tubes until analysis. To ob... more Biological samples are normally collected and stored frozen in capped tubes until analysis. To obtain aliquots of biological samples for analysis, the sample tubes have to be thawed, uncapped, samples removed and then recapped for further storage. In this paper, we report an automated method of sample transfer devised to eliminate the uncapping and recapping process. This sampling method was incorporated into an automated liquid-liquid extraction procedure of plasma samples. Using a robotic system, the plasma samples were transferred directly from pierceable capped tubes into microtubes contained in a 96-position block. The aliquoted samples were extracted with methyl-tert-butyl ether in the same microtubes. The supernatant organic layers were transferred to a 96-well collection plate and evaporated to dryness. The dried extracts were reconstituted and injected from the same plate for analysis by liquid chromatography with tandem mass spectrometry.
European Journal of Clinical Pharmacology, 2001
The pharmacodynamics and pharmacokinetics of omapatrilat, a member of a new class of cardiovascul... more The pharmacodynamics and pharmacokinetics of omapatrilat, a member of a new class of cardiovascular compounds, the vasopeptidase inhibitors, were evaluated in subjects with hepatic cirrhosis (n = 10) and in healthy subjects (n = 10) matched for age, weight, gender and smoking history. All subjects received omapatrilat 25 mg orally once daily for 14 days. Plasma renin and urinary atrial natriuretic peptide (ANP) levels were measured to assess the effect of omapatrilat on cirrhotic subjects. The effect of omapatrilat on blood pressure as well as changes in ANP and plasma renin levels were not altered by hepatic impairment. Pharmacokinetic parameters were determined from plasma omapatrilat concentrations. There were no significant differences between the two subject groups with regard to log-transformed area under the curve or maximum observed plasma concentration. Systemic accumulation was similar in the two groups. These results suggest, based on findings in otherwise healthy cirrhotic subjects, that no adjustment of standard dosing regimens is indicated for hypertensive patients with mild to moderate cirrhosis.
Uploads
Papers by Mohammed Nur Jemal