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Presented here are outsourcing strategies, advantages/challenges and best practices of outsourcing, compliance expectations of a contract laboratory, and development/validation of analytical methods.
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Profiling of impurities in biopharmaceuticals and their associated intermediates and excipients is a regulatory expectation. Since residuals are typically present at low levels in difficult sample matrices, development and validation of assays can be quite challenging. Matrix types can vary greatly due to the fact that sampling at a variety of process steps is required to accurately monitor throughout the production process.
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The FDA has been focusing effort into evaluation of potential adulteration of drug products due to contact with packaging and closure systems, sample delivery devices and components utilized in the manufacturing of the product. Packaging includes components such as vials, caps and stoppers. Drug delivery devices include nebulizers, syringes, medical devices and various types of inhalers. Components utilized during the product manufacturing process include filters, tubing, fittings, connectors, ...
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Formulation is arguably the most critical—and challenging—component of biopharmaceutical drug development, second only to the molecule itself. Formulation's far-reaching consequences help sponsors satisfy the scientific, medical, and regulatory conditions for drug approval and, subsequently, support marketplace success.
A biopharmaceutical formulation consists of active pharmaceutical ingredient and other ingredients that help maintain the drug product's chemical, biochemical, and physical ...
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“Which product in a class should be on formulary?” “What are the economic benefits and risks to adding a product to Tier 2?” Managed care organizations (MCOs) have numerous decisions to make each day. Many of these impact their bottom line. Therefore, it is necessary for the information being used to make the decisions be correct and presented in a fashion that is easy to understand. Pharmacoeconomic models can achieve these goals. This article, the first in a series of three, discusses the ...
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In August 2009 the Food and Drug Administration released a guidance for industry titled, Pharmaceutical Components at Risk for Melamine Contamination. The document, identifying various raw materials that are considered high risk for melamine contamination, recommends monitoring of these raw materials for the presence of melamine prior to release into production. The FDA also provided links to methodology for both melamine and cyanuric acid that could be utilized for this testing. Both GC/MS and ...
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In the manufacture of potent active pharmaceutical ingredients (APIs) and products, there is a need to conduct qualitative and/or quantitative healthbased risk assessments for both occupational and product (patient) safety purposes. When performed from an occupational standpoint, qualitative health-based risk assessments involve the categorization (“banding”) of the API based on toxicity and potency, which provides a measure of relative hazard. Each occupational health categorization is then ...
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Drug innovators, collaborators, licensing partners and the myriad of third parties who handle active pharmaceutical ingredients (APIs) need to take notice when the APIs they are handling have the following properties – clinical doses less than 10 milligrams causing pharmacological or toxic effects in patients or if low doses (less than 1 mg/kg/day) in laboratory animals may potentially be “-genic” (i.e, they are mutagenic, teratogenic, carcinogenic or are reproductive or developmental ...
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Chemical categorization (or banding) of inherent toxicity and potency linked with defined safe work environments including exposure controls has become an integral component of assuring the health and safety of research workers and manufacturing personnel in the pharmaceutical industry but is not a substitute for quantitative risk assessment in the workplace.
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Preclinical Testing for the Medical Device Industry – Material Properties, Leachables/Extractables, and Surface Cleanliness
Jonas Weissenrieder, Ph.D. Pace Analytical Life Sciences Oakdale, Minnesota
Effects of Material and Chemical properties on the biological profile
Chemical and Material Analysis
Why do chemical characterization? Equivalence studies? Economy?
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Qualitative and Quantitative Aspects of Peptide Mapping Using UPLC-UV
Peptide mapping or peptide finger printing produced is characteristic for a particular protein and the UPLC technique can be used to separate a mixture of peptides.
Normally, recombinant proteins are developed for therapeutic purposes. Peptide mapping is used to confirm the primary structure of a protein, identify post-translational modification, to demonstrate generic stability and analyze potential impurities. Any ...
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Since the USP General Chapter <467> on Residual Solvents became effective on July 1, 2008, Lancaster Laboratories has seen a multitude of requests for many different solvent and sample matrix combinations. The new General Chapter applies to both monographed and non-monographed items, including all drug substances, excipients, and products “subject to relevant
controls.” So a number of manufacturers have turned to Lancaster Laboratories for assistance.
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The risk of virus contamination is a feature common to all biotechnology products produced from animal or human sources. Contamination can arise from a source cell line or from adventitious virus introduced during production. The approach to ensuring viral safety includes several complementary approaches, which are laid out in guidelines from the FDA, EMEA and ICH (references 1-4). These guidelines address the viral safety testing requirements for applications for marketing authorization. A ...
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Powder & Porous Materials Characterization
Powder Density in Solid Dosage Forms B by: Martin A. Thomas Ph.D., Director of Business Development Quantachrome Instruments (martin.thomas@quantachrome.com) Both active and inactive (excipient) compounds nal or tapped state. In free-owing powders the are used in the manufacture of solid dosage initial bulk and tapped densities will be more formulations, i.e. tablets and capsules. These similar than in poor owing powders which yield powders possess ...
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An Alternative Approach to Bioequivalence Studies for Semi- Solid Dosage Form Products
Bioequivalence Study Requirements for Semisolid Dosage Form Products
The guidance on Scale-Up and Post Approval Changes (SUPAC)1 for drug products is an informal document representing the best current scientific judgments of the FDA. Its intended purpose is to lower the regulatory burden on the industry while continuing to assure the safety and effectiveness of drug products. SUPAC guidance is developed ...
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At no additional cost to clients, Lancaster Laboratories streamlines Raw Materials testing expressly for certain routine USP and EP tests. Have results in 5 days if compendia methodology and noncustomized documentation formats suit your project needs. And with LabAccess.com, our 24/7 web portal, view all your data such as analysts' notebooks, chromatograms, and individual test results as your projects progress.
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A Database coupled to a Statistical Analysis program is an effective means for establishing a control space, determining process capability of components and correlating leachable levels to extractable levels. Model fit and correlation based on two years of data collection indicate that the two inputs in the model cannot fully model the system.
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A database coupled to a statistical analysis program is an effective means for defining a control space, determining process capability of components, establishing specifications for components and drug product and potentially correlating leachable levels to component extractable levels.
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Synthesis of [14C]-2,6-pyridinedicarboxaldehyde (2) used Selective superoxide dismutase (SOD) mimetics are commercially available 6-bromopicolinic acid as starting potentially useful in pathol. conditions in which there is an material. The 6-bromopicolinic acid was protected as a methyl overproduction of superoxide anion O2-. These conditions ester using refluxing methanol in the presence of trace p-TsOH. include inflammation, ischemia/ reperfusion, shock, The reaction of Methyl ...
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There are no available procedures to synthesize [14C]-ethyl 2-mercaptoacetate (6).1 We developed a safe and conve- nient method to synthesize [14C]-ethyl 2-mercaptoacetate (6). [ 14C]-ethyl 2-mercaptoacetate (6) was synthesized using commercially available [14C]-sodium acetate (1) as the starting material.The mono-bromination of [14C]- sodium acetate (1) was conducted with bromine and sulfur in a sealed reactor.The esterification of [1-14C]- bromoacetic acid (2) with acidic ethanol afforded ...
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H2NOMe 1 Methyl 2-Methoxy-4-Amino-5-Chloro-Benzoate- [Carbonyl-14C] (MMACB-14C)1 is an important intermediate in the synthesis of several Carbon-14 labeled API's. Compound 1 was needed as an intermediate for a synthesis that required seven additional steps that resulted in an overall yield of 36%. A better route was requred to make the synthesis more efficient.
Previous synthesis1,2 of (MMACB-14C) has been performed using 4-amino-2-hydroxy-[carbonyl-14C] benzoic acid as the starting ...
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Triethylenetetraamines (TETA) are important precursors for many diagnostic and therapeutic pharmaceutical agents.
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The 4-nitro-imidazole ring is a very useful precursor used for synthesizing many active pharmaceutical compounds. This is the first attempt to prepare a [14C]-4-nitro- imidazole compound (5). 4-Nitro-imidazole is a pH dependent product.1 The isolation process was modified in our lab to minimize the generation of any residual inorganic impurity during the process.The [14C]-KCN (1) was reacted with sulfur in acetone by Marckwald's method to afford [14C]-thiocyanate (2).The [14C]- thiocyanate (2) ...
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2-Acetoxy-benzoic acid (also known by the common name aspirin) has several applications in fields ranging from pharmaceutical synthesis1 to biology2 and pharmacology.3 Several 2-acetoxybenzoic acid derivatives, which incorpo- rate stable isotopes (i.e. 2H and 13C) have been synthesized,4 however, relatively few radiosyntheses of 2-acetoxybenzoic acid derivatives have been reported.5 Furthermore, the few reported syntheses of radiolabeled 2-acetoxy benzoic acid derivatives typically had low ...
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Diethyl oxalate is an important molecule with various applications including: total synthesis,1 biochemistry,2 materials science,3 and combinatorics.4 While unlabeled diethyl oxalate is commercially available5 and its synthesis has been reported,6 few attempts have been made to synthesize isotopically labeled (i.e. 13C or 14C diethyl oxalate). Furthermore, the few reported syntheses of 13C and 14C radiolabeled diethyloxalate involve several (i.e. 3-5) steps or result in low yields.7 Diethyl ...
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Lysine is an essential amino acid and a critical component of many peptides with an important biological role. Kumar and cowork- ers synthesized a series of lysine containing peptides (Ac-CIYKYY) by functional group modifications in the peptide side chain, to improve the inhibitory potency against Src kinase, which was suspected to cause the development of osteoporosis and in- flammation-mediated bone loss.1 Many of these peptides were synthesized on solid phase resin using Fmoc-Lys(Boc)-OH as ...
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The first time synthesis of L-Cyclohexylglycine- [ring-d11] (L-CHG-d11) and L-Cyclohexylglycine-[1-14C] (L-CHG-1-14C) are described.The resolution of DL-Cyclohexylglycine- [ring-d11] and [1-14C] are achieved by enzymatic process. The chiral purity was determined by converting L-Cyclohexylglycine to Cbz-L-cyclohexylglycine and then checked by chiral HPLC.
L-Cyclohexylglycine-[ring-d11] and L-Cyclohexylglycine-[1-14C] are the key intermediates to prepare a deuterium-11 labeled drug, and ...
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With the global economy in a recession, a vast majority of pharma- ceutical companies are being forced to cut costs and control spending. For most companies this means a reduction in workforce and tighter outsourcing budgets. Companies are left with the same amount of required laboratory testing, but with fewer employees to perform the work in-house. Clients are left searching for value-added programs that will allow them to project all of their outsourcing costs for an entire year in order to ...
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Importance of the eld: Understanding fully the mechanism(s) of action of current and novel anticancer drugs is essential to optimize treatment regimens for oncology patients, to improve or extend drug efcacy and reduce patient side effects. Nucleoside analogues, either alone or in combination with addi- tional therapeutic agents, are an essential part of rst-line and salvage regimens directed against neoplastic diseases. However, many mechanistic studies on this class of drugs have been carried ...
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The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all profes- sional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publica- tion, by five respected experimentalists in diverse sub- fields of biogerontology together with three of ...
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Lancaster Laboratories' Professional Scientific Staffing service has been specifically designed to give you the “non-permanent” workforce you need for anywhere from one year to 10 years or more with no worries about co-employment and at lower costs than fixed headcounts.
Companies have traditionally used two types of staff: their own employ-ees and a temporary workforce. In today's economic environment, few firms are allowed to add employees, so temporary workers are the only option for ...
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Material Category: Food Method Category: Water vapor sorption Instrument Category: Aquadyne DVS
Milk powder is a valuable commodity for industrialized and third world countries. It is widely used in industrialized countries as the basis for powdered infant foods and by the baking and confection industries as a raw ingredient. In developing countries, especially those hit by famines, milk powder is an important source of protein and calories. In both cases transportation charges for an ...
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the stability of a lyophilized igG1 monoclonal antibody was investigated using suboptimal levels of the lyoprotectant, sucrose and the incorporation of the plasticizer, sorbitol. after lyophilization, aggregation and sub-visible particle formation in the reconstituted formulations were evaluated by a number of techniques chosen to encompass a wide range of aggregate sizes. these methods included micro-flow imaging (mfi) to quantify and characterize subvisible particles, dynamic light scattering ...
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The ability to respond to ever-evolving consumer at- titudes, regulatory mandates, and scientic discov- eries requires that manufacturers keep their nger on the pulse of the analytical methodologies required to monitor product safety and quality. In light of the ever- growing number of food and supplement ingredients and complex formulations, the ability to detect unique com- pounds and quantify levels of ingredients at trace levels presents challenges to researchers. The increased efciency and ...
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Human plasma samples spiked with apomorphine and internal standard were extracted using a liquid/liquid extraction technique. Quantitation was performed on a PE Sciex API 3000 LC-MS/MS system with Turbo Ion Spray operating in positive ion Multiple Reaction Monitoring (MRM) mode. Standard curves were produced by linear regression using the peak area ratios of analyte to internal standard and a 1/x weighting.
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The purpose of this study was to validate a sensitive and specific LC-MS/MS assay to determine the human urine levels of dextromethorphan and three metabolites (dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan) in support of metabolite screening studies.
Urine samples were spiked with the analytes and internal standard, hydrolyzed with ß-glucuronidase at 37ºC overnight, and subjected to liquid/liquid extraction. Separation was performed by HPLC utilizing a Zorbax Rx C-8 (2.1 x 150 mm). ...
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Mevalonic acid (MVA) is an important biomarker of cholesterol and bile acid synthesis and resides in two forms in the body, me- valonic acid and mevalonic acid lactone (mevalonolactone).
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The purpose of this study was to validate sensitive and specific Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) methods to determine total cisplatin and carboplatin (as platinum equivalents) in human plasma samples. The method was independently validated for both compounds.
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Previously, four HPLC-MS/MS methods using two columns with multiple injections were used to monitor nine CYP P450 Isozyme activities (Method I). Using this method was not efficient or cost effective. Therefore one optimized HPLC-MS/MS method (two ionization modes) was developed to monitor the activities of all nine Isozymes (Method II).
Frozen pooled (male and female) human liver microsomes were used during the course of the project. Thawed microsomes (~20 mg protein/mL) were diluted 10 fold ...
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A database coupled to a statistical analysis program is an effective means for defining a control space, determining process capability of components, establishing specifica- tions for components and drug product and potentially correlating leachable levels to component extractable levels.
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Caco-2 cells are a widely used in vitro model for studies involving the transepithelial transport of potential drug candidates. The purpose of this study was to compare the transport characteristics of six compounds, all beta- adrenergic receptor antagonists, both individually and combined (“N-in-one”) across Caco-2 cell monolayers. Caco- 2 cells were cultured on Costar Transwell inserts in six-well cell culture plates.The cell supports were polycarbonate membranes with 3-micron pores that had ...
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Concern regarding extractables and leachables has been increasing over the past few years, as evidenced by regulatory guidance documents [1-3]. One means of qualifying a component as being suitable for use in a drug product is to determine the extraction profile of that component in multiple solvents with polarities similar to and bracketing that of the product vehicle. Any observed extractables can then be identified and potential leachable concentrations assessed by a toxicologist to ...
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Apomorphine is under investigation for the treatment of male erectile dysfunction.The tissue distribution of radioactivity was investigated after a single subcutaneous administration of [14C]apomorphine to rats (0.26 mg apomorphine base/kg) and mice (9.2 mg apomorphine base/kg).The animals were exsanguinated immediately after euthanasia followed by collection of selected tissues. Urine, feces, and carcasses were collected at various time intervals postdose.The total radioactivity in the ...
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Apomorphine is under investigation for the treatment of male erectile dysfunction.The mass balance and excretion of radioactivity were investigated after a single subcutane- ous administration of [14C]apomorphine to rats (0.26 mg apomorphine base/kg), mice (9.48 mg apomorphine base/kg) and dogs (0.35 mg apomorphine base/kg). Urine, feces, and cage washes were collected at various time intervals postdose.The total radioactivity was determined using a Beckman LS6000 Liquid Scintillation Counter. ...
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Purpose: To compare the transport of six b-adrenergic receptor antagonists tested individually or combined (“N-in-one”) across Caco-2 cell monolayers prepared by either the Biocoat® 3 to 5-day culture method or the standard 21-day culture method.
Methods: Caco-2 cell monolayers were cultured using either the Biocoat® 3 to 5-day, or the standard 21-day methods. Monolayers prepared with the Biocoat® method were cultured for an additional 2 days (7 days in all) due to low EVOM ...
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Apomorphine is under investigation for the treatment of erectile dysfunction.The enterohepatic recirculation of [14C]apomorphine in Sprague-Dawley rat was investigated. Bile duct-cannulated rats (1M, 1F) were administered a single subcutaneous injection of [14C]apomorphine HCl in saline (containing 1% ascorbic acid and 0.05% sodium metabisulfite) at 2.73 mg free base/kg body weight (90 µCi/kg).The radioactivity recovered in various samples collected totaled 81.86% of dose. Metabolites were ...
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Purpose: J867 is a novel selective progesterone receptor modulator (SPRM).The purpose of this study was to investigate the absorption and excretion of radioactivity after administration of a single intravenous (IV) or oral (PO) dose of [14C]J867 to rats, mice and monkeys.
Methods: [14C]J867 was administered at ~5 mg/Kg BW in a single IV or PO dose to noncannulated or bile duct-cannulated Sprague-Dawley rats, CD-1 mice, and Cynomolgus monkeys. Urine, feces and bile were collected at various ...
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LC-MS analysis of monkey liver microsomal incubations of the drug candidate J867 in the presence of GSH demonstrated a metabolite with a mass corresponding to a glutathionyl conjugate that must be formed via a 2-electron oxidation process.The LC-MS/MS data were consistent with either a phenyl or a C-oximino conjugate. In order to investigate the site of conjugation, the corresponding incubations were carried out with J867-d (phenyl ring).
Pooled monkey liver microsomal incubations ...
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To develop and validate an LC-MS/MS method for the determination of cortisol in human saliva containing 1.5 mM citric acid. Among other functions, cortisol serves to help the body manage stress and has been termed “the stress hormone” because it is also secreted in higher levels during the body’s response to stress. Therefore, the levels of cortisol can be used as a biomarker and pharmacodynamic indicator to support pharmacokinetic findings. Previous reported methodologies have only focused on ...
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Common literature methods for determining formalde- hyde in air and water are based on derivatizing formalde- hyde first, by the use of either 2,4-dinitrophenylhydrazine (DNPH) or 2,3,4,5,6-pentafluorobenzyloxyamine (PFBOA) and then quantitating the resulting hydrazone or oxime. We report general procedures for the derivatization and determination of total extractable formaldehyde as well as leachable formaldehyde in hydroxypropyl methylcellulose (HPMC) capsules. Trapped formaldehyde in HPMC ...
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Flow cytometry has replaced the Ham test as the gold standard technique for diagnosing patients with Paroxysmal Nocturnal Haemoglobinuria (PNH). This report highlights the significant contributions flow cytometry has made in defining phenotypes of PNH.
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Aptuit Informatics 29219 Canwood Street, Suite 120 Agoura Hills, CA 91301 USA Tel: +1 818.879.0075 Fax: +1 818.879.7303
Information contained herein is proprietary to Aptuit Informatics, Inc. Ideas, concepts, designs, methods and the like are the intellectual property of Aptuit Informatics, Inc. and as such are protected by US and international copyright laws as well as US and international laws governing the protection of and trade in intellectual properties. This document may not be ...
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Knowledge is power. When it comes to choosing your suppliers for buying instruments, equipment or services, are you effectively utilizing maintenance and service information to help you make wise purchasing decisions? Do you know how well your suppliers are performing? Do you know how your manufacturers and service providers compare to each other in quality and service delivery? Do you have the tools and information to help you leverage the volume of your purchasing power and negotiate better ...
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Asset Management Organizations today are under tremendous pressure to increase productivity and efficiency, reduce total cost of ownership, and focus on core business competencies. To meet these business objectives, many are looking to external business partners to manage non-core business competencies, especially in the area of instrument and equipment management, service and support. In today’s complex corporate environment, it can be very difficult for decision makers to determine an asset ...
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Conducting comprehensive metabolism studies has long been an essential component of a preclinical drug development program. However, numerous factors — including the increased development of protein-derived drugs and the expanded interest in the role of metabolites in safety assessment — are having a significant impact on the regulatory mandates, scope of studies and methodologies employed. In addition, increased scientific and agency scrutiny pertaining to the bioanalytical method validation ...
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Biotech was “born” in the 1970s. Since that time innovation by biotech pioneers has brought more than 200 medicines and vaccines to fruition for difficult-to-treat indications including oncology, HIV/ AIDs, diabetes, and immune disorders.
Biotech is poised to capitalize on the current challenges confronting Big Pharma: looming patent expirations on blockbuster medicines and a dearth of new compounds in the pipeline to replace them. Current pharmaceutical business models are in the doldrums ...
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An LC-MS/MS method was developed and validated for the determination of aripiprazole (OPC-14597) and its metabolites in human urine.The method employed C-18 SPE, followed by LC-MS/MS. Aripiprazole is under investigation for use in the treatment of schizophrenia.
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An LC-MS/MS method was developed and validated for the determination of cilostazol (OPC-13013) and its metabolites in human plasma.The method employed liquid-liquid partition, C-18 SPE, followed by LC-MS/MS. Cilostazol is under investigation for use in the treatment of intermittent claudication.
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Noroxycodone Abstract An HPLC-MS/MS method was developed and validated for oxycodone and two of its active metabolites, oxymorphone and noroxycodone, in plasma at ABC-Europe in the range of 0.200 - 100 ng/mL.The method was subsequently validated at ABC-US.
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A sensitive, simultaneous and rugged LC-MS/MS method was developed and validated for the quantitation of cortisol and 6ß-hydroxycortisol in human urine. Changes in ratio of 6ß-hydroxycortisol/cortisol in response to a drug is an indi- cation of induction/inhibition of CYP3A enzymes.
Calibration curves and QC samples were prepared in a surrogate matrix. Endogenous levels, recovery of spiked samples and stability data were determined using human urine.
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Buprenorphine (an opioid mixed agonist-antagonist) has been shown to be a safe and effective treatment of opiate dependence. Norbuprenorphine is a major metabolite of buprenorphine. Quantitative analysis is required for the determination of buprenorphine and its major metabolite, norbuprenorphine in the preclinical studies.
A sensitive and specific HPLC-MS/MS assay method for the simultaneous determination of buprenorphine and its metabolite, norbuprenorphine, in beagle plasma was therefore ...
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Historically, vaccines are medicines that deliver or generate antigens that induce specic, active, and protective immunity against infectious diseases. Antigens stimulate the immune system to activate cells and organs that induce active immunity, characterized by production of antibodies (humoral immunity) and/or cytotoxic T-cells (cell mediated immunity). Vaccines “train” the body’s immune system to ght infection or disease. Vaccines have eradicated smallpox, practically eliminated polio, and ...
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An HPLC-MS/MS method was developed and validated for rifabutin in plasma with a linear range of 5.00 to 800 ng/mL. Rifabutin is a semisynthetic antibacterial agent for use against diseases such as Mycobacterium-avium complex in HIV-positive patients. The HPLC-MS/MS method developed was validated for the determination of rifabutin in human plasma.
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Alprazolam and midazolam are known CYP3A4 inhibitors and are used in the investigation of potential drug-drug interactions in clinical studies.1 A sensitive and specific HPLC-MS/MS assay method for the simultaneous determination of alprazolam, midazolam and their α-hydroxy metabolites in human plasma was therefore developed and validated according to the current industry guidelines.2 The calibration range for the method is 0.100 to 10.0 ng/mL for alprazolam and midazolam; and 0.200 to 10.0 ...
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Oxycodone (a semi-synthetic derivative of morphine) is a narcotic analgesic or a narcotic painkiller used to relieve moderate to severe pain. Quantitative analysis is required for the determination of oxycodone and two of its metabolites, noroxycodone and oxymorphone in the clinical studies. A sensitive and specific HPLC-MS/MS assay method for the determination of oxycodone and two of its metabolites, noroxycodone and oxymorphone, in human plasma was therefore developed and validated according ...
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LC-MS/MS and ICP-AES methods were developed and validated for the quantitation of Gadoversetamide (MP-1177) in human urine. For LC-MS/MS, human urine containing MP-1177 and the internal standard, MP-2077, was centrifuged.The supernatant was analyzed directly. For ICP-AES, human urine containing MP-1177 was acidified with HCl and analyzed directly for gadolinium.
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Apomorphine (5,6,6a,7-tetrahydro-6-methyl-4H- dibenzo[de,g]quinoline-10,11-diol) is a dopamine receptor agonist under development for the treatment of erectile dysfunction.The purpose of this study was to characterize the in vitro metabolism of apomorphine by hepatocytes from human, rat, and dog. Solutions of 14C-labeled and nonradiolabeled apomorphine were incubated with primary hepatocytes at 1, 2, and 4 hours. Samples of the incubation media were analyzed by HPLC with radiodetection. ...
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A sensitive and specific LC-MS/MS method was developed for the quantitation of 7-hydroxycoumarin, resorufin, hydroxytolbutamide, 4' hydroxymephenytoin, 6ß- hydroxytestosterone, dextrorphan, 6-hydroxychlorzoxazone and 12-hydroxylauric acid metabolites generated by cytochrome P450 enzymes using standard probe substrates.
The analysis was conducted using a calibration curve prepared by fortifying metabolites in the incubation buffer only.The method performance was validated by analyzing quality ...
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LC-MS/MS and ICP-AES methods were developed and validated for the quantitation of Gadoversetamide (MP-1177) in human plasma. For LC-MS/MS, human plasma containing MP-1177 and the internal standard, MP-2077, was subjected to ultrafiltration.The filtrates were analyzed directly.
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To develop and validate a sensitive and reproducible LC-MS/MS assay for the determination of cyclic guanosine monophosphate (cGMP) in potassium EDTA human plasma containing aprotinin. cGMP is know to relax vascular smooth muscle tissue which leads to vasodilation and increased blood-flow to the tissue. Drugs found to increase cGMP levels have been investigated and developed. Monitoring the levels of cGMP in human plasma can serve as a biomarker for these therapeutic areas. The methodology ...
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Erythromycin is a known CYP3A4 inhibitor and is used in the investigation of potential drug-drug interactions in clinical studies.1 A specific HPLC-MS/MS assay method for the determination of erythromycin in human plasma was developed and validated according to the current industry guidelines.2
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Erythromycin is a known CYP3A4 inhibitor and is used in the investigation of potential drug-drug interactions in clinical studies.1 A specific HPLC-MS/MS assay method for the determination of erythromycin in human plasma was developed and validated according to the current industry guidelines.
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A sensitive and rugged HPLC-UV method was developed and validated for the quantitation of 2,3-dihydroxy- benzoic acid (DHBA) in the linear range of 10-1000 μg/mL in rat, dog, and human plasma. DHBA is a metabolite of 2,3-diacetoxybenzoic acid (DABA).
2,3-dihydroxybenzoic acid (2,3-DHBA) is a product of salicylate metabolism produced through the action of the hydroxyl radical. This compound can be used as a marker to assess hydroxyl radical formation both in vitro and in vivo. In addition, ...
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Budesonide is an anti-inflammatory, synthetic corticosteroid used for the treatment of asthma by oral inhalation.The objective was to validate a sensitive and specific HPLC-MS/ MS assay to determine budesonide in human plasma for support of Sheffield Pharmaceutical clinical trials. An automated 96-well HPLC-MS/MS assay method for the determination of budesonide in human plasma was therefore developed and validated according to the current industry guidelines.1 The calibration range for the ...
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Octreotide is indicated at low doses for the treatment of carcinoid tumors.Therefore, a comparison of LC-MS/MS and RIA assays was performed to determine the most suitable method for the quantitation of Octreotide in rat plasma.
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A specific and sensitive HPLC-MS/MS method was developed and validated for the quantitation of PT-141 for a linear range of 0.500-100 ng/mL in human plasma and 5.00-2500 ng/mL in rat plasma.
PT-141 is an analog of α-melanocyte-stimulating hormone (α -MSH) with agonist activity at the melanocortin receptor (MCR) subtypes 1, 3, 4, & 5. Melanocortin peptides have been implicated in several behaviors including grooming, yawning, food intake, and penile erection.1 Rodent and primate studies ...
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The objective was to validate a sensitive and specific HPLC-MS/MS assay to determine the concentration of PL-2299 in human, rat and beagle plasma for support of Palatin Technologies, Inc. preclinical and clinical studies.
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Investigation of the metabolic pathways of new drug candi- dates using both in vitro and in vitro methods has become very important during drug development . The goal of this study was to profile and identify metabolites of apomor- phine, which is under investigation for the treatment of male erectile dysfunction, in both in vitro and in vitro gener- ated samples.
In vitro: The metabolism of apomorphine in vitro was investi- gated after a single subcutaneous dose of [14C]apomorphine at 0.34 ...
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Amlexanox is used in the treatment of minor aphthous ulcers (canker sores). A specific HPLC-FL assay method for the determination of amlexanox in human serum was therefore developed and validated according to the current industry guidelines.1 The calibration range for the method is 5-250 ng/mL.
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Picolinic acid is an endogenous biologically active molecule which serves as the body's natural chelator of certain transition metals, such as zinc. Picolinic acid is a terminal metabolite generated from the catabolism of tryptophan.The circulating levels of picolinic acid are proposed to change in certain pathological conditions and during therapy.
A sensitive and specific HPLC-MS/MS method was developed and validated for the quantitation of pico- linic acid in the linear range of 10-1000 ...
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Nolatrexed dihydrochloride, a thymidylate synthase inhibitor, is a novel oncology compound that is being developed to treat several different cancers, with an initial emphasis in hepatocellular carcinoma (liver cancer). Nolatrexed dihydrochloride is currently in a Phase III trial for the treatment of unresectable hepatocellular carcinoma.
A sensitive and specific HPLC-UV method was developed and validated for the quantitation of nolatrexed dihydrochloride in the linear range of 0.250- 20.0 ...
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A sensitive radioimmunoassay (RIA) method was validated for the determination of octreotide in male rat plasma using reagents provided in the kits by Peninsula Laboratories, Inc. (Belmont, CA). The components provided in the RIA kit were used to validate octreotide in male rat plasma over a concentration range of 80-1280 pg/mL.
Octreotide mimics the action of somatostatin, a naturally occurring hormone found in the brain and gastrointestinal tract. Somatostatin is one of several substances ...
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Apomorphine is under investigation for the treatment of male erectile dysfunction.The disposition and metabolism of apomorphine were investigated after a single subcutaneous dose of [14C]apomorphine (0.34 mg apomorphine base/kg) to a bile duct-cannulated male dog. A total of 92.2% of the administered dose was recovered: 0.1% in plasma, 38.2% in bile, 51.2% in urine, 2.1% in feces, and 0.7% in cage wash.The radioactivity in plasma reached a maximum (190 ng/g) at 100 minutes postdose. Unchanged ...
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Ajulemic acid, a non-psychoactive synthetic cannabinoid derivative of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), has a chemical structure amenable to high pH conditions for HPLC-tandem mass spectrometric analysis.
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Enoximone is a selective PDE-3 inhibitor currently in Phase III development for the treatment of advanced chronic heart failure. Enoximone is metabolized to the primary metabolite, enantiomeric enoximone sulfoxide, and it is important to determine if this conversion is stereoselective.
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Introduction/Objectives:
-J867 is a novel selective progesterone receptor modulator (SPRM).
-Investigate the in vitro metabolism of J867 using hepatocytes and liver microsomes from male and femal human and various animal species.
-Characterize radioactivity in microsome and hepatocyte metabolites using HPLC-radiochromatography.
-Tentatively identify J867 metabolites by LC-MS/MS generated during the conduct of the microsome and hepatocyte studies.
-Elucidate a metabolic pathway for J867 ...
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Introduction / Objectives:
• J867 is a novel selective progesterone receptor modulator (SPRM).
• The disposition and metabolism of J867 were investigated after intravenous (IV) or oral (po) administration of [14C]J867 to male and female bile duct-cannulated Sprague-Dawley rats and CD-1 mice.
• Characterize the radioactivity in bile using HPLC- radiochromatography.
• Tentatively identify J867 metabolites by LC-MS/MS generated during the conduct of the bile duct-cannulated mouse and rat ...
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Apomorphine is under investigation for the treatment of erectile dysfunction. The excretion and metabolism of apomorphine were investigated after administration of a single sublingual dose of [14C]apomorphine (1.94 mg, approximately 80 µCi 14C, as an aqueous solution) to six healthy male subjects. Whole blood, plasma, urine and feces samples were collected at designated times during a 7-day postdose period and were analyzed for total radioactivity by liquid scintillation counting. Plasma, urine ...
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Apomorphine (5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo [de,g]quinoline-10,11-diol) is a dopamine receptor agonist under development for the treatment of erectile dysfunction.The purpose of this study was to characterize the binding of apomorphine to plasma proteins from humans and various animal species (mouse, rat and dog) of each gender.The binding of apomorphine to plasma proteins was evaluated using equilibrium dialysis.The binding of apomorphine to human serum albumin and α1-acid ...
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Oxaliplatin is a platinum containing compound that is currently used in pharmacotherapy of metastatic colorec- tal cancer and is of interest to many in the field of oncol- ogy. It is approved by the Food and Drug Administration (FDA) to be used together with other drugs as adjuvant treatment for stage III colon cancer.
A specific ICP-MS assay method for the determination of platinum from oxaliplatin in human plasma ultrafiltrate was developed and validated (calibration range of 0.05-2.50 ...
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A preliminary study was conducted to determine the binding of [14C]warfarin to plasma proteins of human and laboratory animal species and protein solutions using ultrafiltration. [14C]Warfarin was 99.1, 98.9, 97.7, 94.2, 91.9 and 89.1% bound to plasma proteins of human, monkey, rat, rabbit, dog and mouse, respectively (average of the two genders). [14C]Warfarin was highly bound to HAS (99.0%) and only moderately bound to AGP (60.8%).
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Apomorphine is under investigation for the treatment of male erectile disfunction.
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Purpose: To characterize the cytochrome 450 (CYP450) isoenzymes involved in the metabolism of brinzolamide by human liver microsomes using 1) Correlation analysis with typed human liver microsomes from individual livers, and 2) Inhibition with CYP450 isoenzyme-selective chemical inhibitors.
An LC-MS/MS method was developed for the quantitation of N-desethyl brinzolamide, O-desmethyl brinzolamide, and N-desmethoxypropyl brinzolamide in samples from human liver microsomal incubations. ...
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Since EDC has become a valid alternative for paper-based trials, we are more often confronted with the problem of trial specific database structures, which are inherent to EDC. The lack of standards makes inter-department and inter-organizational collaboration difficult. A standard database structure, as prepared by the SDS team of CDISC would certainly facilitate the collection, exchange, reporting and submission of clinical data.
Ideally, the EDC provider delivers a standard structure. ...
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