This document describes an automated method for measuring 71 drugs of abuse in urine and oral fluid samples using online solid phase extraction liquid chromatography tandem mass spectrometry (ITSP-LC/MS/MS). The method uses ITSP cartridges to clean and concentrate samples so that drugs can be detected down to 1 ng/mL with high throughput of processing two 96-well plates overnight per instrument. The method is simple, robust, and can be performed by technicians with minimal training. Total analysis time from sample loading to results is 4.5 minutes per sample.
This randomized, double-blind, placebo-controlled clinical trial tested whether a genetically-informed biomarker of nicotine metabolism (nicotine metabolite ratio or NMR) could predict responses to nicotine patch or varenicline for smoking cessation. 1246 smokers were randomized to receive placebo, nicotine patch, or varenicline. The primary outcome was 7-day point abstinence at end of treatment. For normal metabolizers, varenicline was more effective than nicotine patch, but for slow metabolizers there was no difference. Secondary outcomes and side effects also varied by treatment and NMR group. The authors concluded the NMR may help direct therapy selection to increase quit rates while decreasing side effects.
SUV- standardised uptake values in pet scanningtodd_charge
Standardized uptake values (SUVs) are a quantitative measure of fluorodeoxyglucose (FDG) uptake in tissue, but they have many limitations and variables that must be accounted for. SUVs are influenced by factors like patient size, measurement time, plasma glucose levels, and scanner specifications. While SUVs provide a quantitative evaluation of tumor metabolism and can help distinguish malignant from benign lesions, they should be used cautiously and considered alongside a subjective analysis. SUVs may be helpful but are not definitive, and are only comparable when measured using the same scanner and protocols within an institution.
A new Standard Uptake Values (SUV) Calculation based on Pixel Intensity ValuesPawitra Masa-ah
S. Soongsathitanon, et al., "A new Standard Uptake Values (SUV)
Calculation based on Pixel Intensity Values," INTERNATIONAL JOURNAL of MATHEMATICS AND COMPUTERS IN SIMULATION , NAUN, Issue 1, Volume 6, pp 26-33, 2012 .
http://www.naun.org/journals/mcs/
بعض (وليس الكل) ملخصات الأبحاث الجيدة المنشورة فى بعض المجلات الجيدة وفيها تنوع من الافكار الابحاث الابتكارية التى يخدم فيها علوم الحاسبات فيها - انها تطبيقات حياتية
A prospective randomised trial of the optimal dose of mannitol for intra operative Brain relaxation in patients undergoing craniotomy for supratentorial brain tumour : Hyungseok et al.
Journal club :Neurosurgical conference , KKU.
I should this paper to review how they study of the optimum dosage of mannitol in neurosurgical operation.
Thecomparison methods of amphetamines detection in urine samples in Thammasat...kridsada31
Thecomparison methods of amphetamines detection in urine samples in ThammasatUniversity hospital, Pathumtaniprovince.
KridsadaSirisabhabhornSupapornPumpaNarumonSereekhajornjaruand PalakornPuttarak
Department of Medical Technology Laboratory, ThammasatUniversity Hospital Pathumtani, Thailand
The document discusses target controlled infusion (TCI) for intravenous anesthesia. TCI uses pharmacokinetic models and computer controlled infusion pumps to maintain stable plasma or effect-site concentrations of anesthetic drugs. It achieves this by simulating drug concentrations based on dosage and continually adjusting the infusion rate. TCI allows titration of drugs to clinical effects and precise control of drug levels throughout a procedure. Accuracy depends on how well the pharmacokinetic model matches an individual patient. Future improvements include accounting for individual patient factors, multidrug interactions, and closed-loop systems.
This randomized, double-blind, placebo-controlled clinical trial tested whether a genetically-informed biomarker of nicotine metabolism (nicotine metabolite ratio or NMR) could predict responses to nicotine patch or varenicline for smoking cessation. 1246 smokers were randomized to receive placebo, nicotine patch, or varenicline. The primary outcome was 7-day point abstinence at end of treatment. For normal metabolizers, varenicline was more effective than nicotine patch, but for slow metabolizers there was no difference. Secondary outcomes and side effects also varied by treatment and NMR group. The authors concluded the NMR may help direct therapy selection to increase quit rates while decreasing side effects.
SUV- standardised uptake values in pet scanningtodd_charge
Standardized uptake values (SUVs) are a quantitative measure of fluorodeoxyglucose (FDG) uptake in tissue, but they have many limitations and variables that must be accounted for. SUVs are influenced by factors like patient size, measurement time, plasma glucose levels, and scanner specifications. While SUVs provide a quantitative evaluation of tumor metabolism and can help distinguish malignant from benign lesions, they should be used cautiously and considered alongside a subjective analysis. SUVs may be helpful but are not definitive, and are only comparable when measured using the same scanner and protocols within an institution.
A new Standard Uptake Values (SUV) Calculation based on Pixel Intensity ValuesPawitra Masa-ah
S. Soongsathitanon, et al., "A new Standard Uptake Values (SUV)
Calculation based on Pixel Intensity Values," INTERNATIONAL JOURNAL of MATHEMATICS AND COMPUTERS IN SIMULATION , NAUN, Issue 1, Volume 6, pp 26-33, 2012 .
http://www.naun.org/journals/mcs/
بعض (وليس الكل) ملخصات الأبحاث الجيدة المنشورة فى بعض المجلات الجيدة وفيها تنوع من الافكار الابحاث الابتكارية التى يخدم فيها علوم الحاسبات فيها - انها تطبيقات حياتية
A prospective randomised trial of the optimal dose of mannitol for intra operative Brain relaxation in patients undergoing craniotomy for supratentorial brain tumour : Hyungseok et al.
Journal club :Neurosurgical conference , KKU.
I should this paper to review how they study of the optimum dosage of mannitol in neurosurgical operation.
Thecomparison methods of amphetamines detection in urine samples in Thammasat...kridsada31
Thecomparison methods of amphetamines detection in urine samples in ThammasatUniversity hospital, Pathumtaniprovince.
KridsadaSirisabhabhornSupapornPumpaNarumonSereekhajornjaruand PalakornPuttarak
Department of Medical Technology Laboratory, ThammasatUniversity Hospital Pathumtani, Thailand
The document discusses target controlled infusion (TCI) for intravenous anesthesia. TCI uses pharmacokinetic models and computer controlled infusion pumps to maintain stable plasma or effect-site concentrations of anesthetic drugs. It achieves this by simulating drug concentrations based on dosage and continually adjusting the infusion rate. TCI allows titration of drugs to clinical effects and precise control of drug levels throughout a procedure. Accuracy depends on how well the pharmacokinetic model matches an individual patient. Future improvements include accounting for individual patient factors, multidrug interactions, and closed-loop systems.
Wright-Williams et al (2013) Effects of vasectomy & buprenorphine on cort and...Johnny Roughan
This study evaluated the effects of vasectomy surgery and buprenorphine treatment on behavior and stress levels in two strains of mice. Surgery caused abnormal behaviors and increased stress hormones in feces. Higher-dose buprenorphine reduced pain behaviors in one strain based on manual scoring, but lower doses and automated scoring were less effective due to buprenorphine increasing general activity levels. The study found manual pain-specific scoring to be better than activity monitoring for assessing analgesic drugs in mice after surgery.
Chromatography is a technique for separating various inorganic and organic compounds. It is one of the separation techniques used as differential migration. It is more advantageous over conventional separating methods such as crystallization, solvent extraction and distillation. The purpose of presentation is to present various chromatographic techniques included a few advanced forms such as FC, HPLC,UPLC and UPCC (Super Critical chromatography).These are rapid forms of chromatographic techniques based on air pressure driven, optimized for rapid and precise separation of an organic compound.
1) The study aimed to audit adherence to guidelines for intravenous unfractionated heparin (IVUH) administration and monitoring of activated partial thromboplastin time (aPTT) at a hospital.
2) They found that only 79% of patients had baseline tests recorded before treatment, and less than half received the recommended initial bolus dose based on weight.
3) Dose adjustments were often not made according to the trust's protocol, with 57% deemed inappropriate, and extreme aPTT values were related to prior inappropriate adjustments. The study highlights the need for improved guideline adherence when using this high-risk drug.
Analytical Considerations When Monitoring Pain Medications by LC-MS/MSDavid Masters-Moore
Laboratory urine drug testing of patients on chronic opioid therapy requires providing a large test menu of medications commonly prescribed for this population as well as metabolites and illicit substances. It has been shown that liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred method to analyze urine specimens for these substances.
Purpose of the study: To describe the challenges and some of the techniques to validate the analytical procedures used to identify and quantify these medications and substances.
Methods: Using data obtained from testing over one million specimens, the authors developed a proposed test menu. Potential isobaric interferences were established by using literature references. A list of potentially interfering medications was obtained by using the proposed test menu and the most commonly prescribed medications. Finally, criteria were designed to detect possible carryover.
Results: The LC-MS/MS instrumentation eliminated all potential interferences and provided quantitative data over the test range needed to monitor these patients. Carryover could be eliminated by setting the carryover thresholds for each analyte.
Conclusions: Reference laboratories utilizing LC-MS/MS technology to conduct urine drug testing for pain clinicians should employ specific techniques described in this study to develop an optimal test menu and validate procedures that include isolating retention times for isobaric compounds, identifying interfering substances including impurities in medicinal and illicit substance preparations, monitoring ion suppression, and avoiding carryover.
This study evaluated intensity modulated radiotherapy (IMRT) plans for 10 simulated tracheal tumor patients that accounted for optimization convergence errors (OCEs). Plans optimized without OCE corrections showed significantly more target dose inhomogeneity compared to plans optimized using a method to correct for differences between the optimization and dose calculation algorithms. Correcting for OCEs resulted in IMRT plans with more conformal and homogeneous target dose distributions for intraluminal tracheal tumors.
ICH guidelines provide standards for toxicity studies to ensure safe, effective, and high quality pharmaceutical products. Guideline S3A deals with conducting toxicity studies and quantifying exposure. General principles include quantifying exposure levels in different species and sexes using plasma concentration or area under the curve. Toxicokinetic studies should be performed to determine metabolite levels and justify dose levels. Reporting should include detailed toxicokinetic data and evaluation. Toxicokinetics are assessed in various toxicity studies including single dose studies, repeated dose studies, genotoxicity studies, carcinogenicity studies, and reproductive toxicity studies.
This is the presentation on Role of advancement in instrumentation in pharmacodynamic evaluation of drugs
in clinical trials.
CONTENTS
Concept of medical instrument and instrumentation
Centrifuge
PCR
HPLC
Flow cytometry
Mass SPECTROMETRY
Minimally invasive technologies in PD
Conclusion
This document presents the development and validation of a new RP-UPLC method for the simultaneous estimation of lamivudine, tenofovir, and efavirenz in tablet dosage forms. The optimized method uses a C18 BEH column, a mobile phase of 35% phosphate buffer (pH 3.0) and 65% methanol, and detects the drugs at 260 nm. The method was validated per ICH guidelines and found to be specific, precise, accurate, linear, robust, and stability-indicating for the simultaneous analysis of the drugs without interference from excipients. The developed and validated RP-UPLC method provides a simple, rapid, and economical approach for the routine quality control analysis of fixed
The document describes the development of an enhanced performance test mix for monitoring high-throughput LC/MS systems used in pharmaceutical analysis. The test mix was designed to:
1) Consist of 8 drug-like compounds selected from a pool of 137 compounds to represent typical properties like mass, hydrophobicity, and charge state.
2) Monitor key aspects of LC/MS performance including separation (gradient, flow, pH), detection (UV, ELS, MS signal), and mass accuracy across different conditions.
3) Provide diagnostic information about the likely cause of any errors based on differences observed in test mix results compared to historical data.
Differential spectrophotometric method for estimation and validation of Verap...roshan telrandhe
The aimed of current research to development of the simple, rapid and sensitive Differential spectrophotometric method for the estimation of Verapamil in tablet dosage form. In this method two medium was use acid and alkaline and the difference spectrum was calculated. 0.1N HCL and 0.1N NaOH was used in this differential method. The λmax 278, beeers law limits 525µg/ml, regression equation Y= 0.024x-0.009, slope 0.024, intercept 0.09, correlation coefficient (r2) 0.998, %RSD <1.5, % Recovery (Tablet) 100.46% was shows the good efficacy and results. This method future scope in quality control of the verapamine in simple, precise and economically and it recommended for the routine drug quality analysis investigation.
This document discusses approaches for identifying somatic mutations from cancer sequencing data using multiple mutation callers. It compares several popular mutation callers, explores a simple consensus approach, and proposes an integrated ensemble approach. The ensemble approach applies multiple callers, filters using GATK, and assigns a ranking score to variants based on validation rates to generate a high-confidence list of somatic mutations. This strategy aims to leverage the strengths of different callers to improve accuracy over any single caller.
Therapeutic drug monitoring (TDM) involves measuring drug levels in a patient's blood or plasma to ensure concentrations remain within a therapeutic range. TDM is useful for drugs with a narrow therapeutic window, high individual variability in effects, or when clinical effects are difficult to observe. Factors like dosage, sampling time, drug interactions, and individual physiology can impact drug levels and require monitoring to optimize treatment and avoid toxicity. Common methods to measure drug concentrations include chromatography techniques coupled with mass spectrometry, as well as various immunoassays.
Recent Advances in Respiratory Physiotherapy 2.pptxSaumyaKine
Recent advances in Respiratory physiotherapy covers a comprehensive aspect of newer technologies helpful in the field of pulmonary physiotherapy. Useful for MPT students. Has articles added up for reference.
Prescription event monitoring and record linkage systemRumana Hameed
PEM is a method of pharmacovigilance that studies drug safety in real-world clinical practice. It involves collecting prescription data for new drugs and surveying prescribers about patient outcomes. Advantages include a large national scale and obtaining real-world safety data. Record linkage systems combine different healthcare records to efficiently study relationships between drug exposure and health outcomes. Claims databases contain prescription and medical claims information but may lack clinical details, while medical record databases provide more clinical data but only for illnesses that were medically attended to.
UV Spectrophotometric Method Development and Validation for Quantitative Esti...Sagar Savale
U.V Spectrophotometric method have been widely employed in determination of Curcumin in a mixture or fixed dose combination. For the ternary mixture containing Curcumin, no spectrophotometric method for evaluation has been reported so far. Thus our aim is to develop method for Curcumin estimation in ternary mixture using U.V spectrophotometry.
S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES
S3B: PHARMACOKINETICS: GUIDANCE FOR REPEATED DOSE TISSUE DISTRIBUTION STUDIES
This document describes the development and validation of a new spectrofluorimetric method for the estimation of desvenlafaxine succinate in bulk and pharmaceutical formulations. Key points:
1) The method utilizes the native fluorescence of desvenlafaxine succinate with an excitation wavelength of 274 nm and emission wavelength of 305 nm in pH 6 phosphate buffer.
2) The method was found to be linear over a concentration range of 100-900 ng/ml. Validation studies established the method's accuracy, precision, selectivity, robustness and ruggedness according to ICH guidelines.
3) The developed method was successfully applied to the analysis of desvenlafaxine succinate in commercial extended-
This document summarizes a study comparing traditional immunoassay screening followed by confirmation using solid phase extraction and gas chromatography/mass spectrometry (SPE/GC-MS) or liquid chromatography/tandem mass spectrometry (LC-MS/MS) to a new method using automated solid phase extraction coupled to high performance liquid chromatography and tandem mass spectrometry (SPE/HPLC/MS/MS) for analyzing urine samples submitted for driving under the influence (DUI) cases. In the study, 106 samples previously confirmed positive by the traditional methods were re-analyzed using the new automated SPE/HPLC/MS/MS method. The new method found additional positive results for THC, amphetamines, benzodiazep
This document summarizes a study comparing traditional immunoassay screening followed by confirmation using solid phase extraction and gas chromatography/mass spectrometry (SPE/GC-MS) versus automated solid phase extraction high performance liquid chromatography tandem mass spectrometry (SPE/HPLC/MS/MS) for analyzing urine samples submitted for driving under the influence (DUI) cases. 106 samples previously confirmed positive by the traditional methods were re-analyzed using the automated SPE/HPLC/MS/MS system. More drugs were detected using the automated system, including 12 additional THC cases, 4 additional amphetamine cases, 6 additional benzodiazepine cases, and 3 additional cocaine cases. The automated system was able to process samples faster and at
Automated Chromatographic Solid-Phase Extraction Using an Autosampler _ Ameri...Rick Youngblood
1) Automated solid-phase extraction (SPE) using an autosampler increases sample throughput compared to manual SPE. An autosampler transports micro SPE cartridges containing chromatographic media and performs conditioning, loading, washing, and elution steps directly on an LC/MS or GC/MS system.
2) Precise syringe pump flow control over the packed sorbent bed in micro SPE cartridges enables optimal separations. This results in systematically high and precise analyte recoveries not typically achieved with other SPE methods.
3) Integrating SPE directly into LC/MS or GC/MS analysis as an online workflow using an autosampler achieves higher quality results than a two-step robotic process
This document provides an intermediate course for lab personnel on using an ITSP PAL autosampler. It discusses (1) using PAL Loader software to manage firmware, (2) using PAL Object Manager software to manage objects, (3) using the local terminal to manage objects and positions, (4) important ITSP concepts, and (5) regular maintenance procedures. The document includes screenshots and step-by-step instructions for processes like teaching positions, verifying positions, and troubleshooting firmware issues.
Wright-Williams et al (2013) Effects of vasectomy & buprenorphine on cort and...Johnny Roughan
This study evaluated the effects of vasectomy surgery and buprenorphine treatment on behavior and stress levels in two strains of mice. Surgery caused abnormal behaviors and increased stress hormones in feces. Higher-dose buprenorphine reduced pain behaviors in one strain based on manual scoring, but lower doses and automated scoring were less effective due to buprenorphine increasing general activity levels. The study found manual pain-specific scoring to be better than activity monitoring for assessing analgesic drugs in mice after surgery.
Chromatography is a technique for separating various inorganic and organic compounds. It is one of the separation techniques used as differential migration. It is more advantageous over conventional separating methods such as crystallization, solvent extraction and distillation. The purpose of presentation is to present various chromatographic techniques included a few advanced forms such as FC, HPLC,UPLC and UPCC (Super Critical chromatography).These are rapid forms of chromatographic techniques based on air pressure driven, optimized for rapid and precise separation of an organic compound.
1) The study aimed to audit adherence to guidelines for intravenous unfractionated heparin (IVUH) administration and monitoring of activated partial thromboplastin time (aPTT) at a hospital.
2) They found that only 79% of patients had baseline tests recorded before treatment, and less than half received the recommended initial bolus dose based on weight.
3) Dose adjustments were often not made according to the trust's protocol, with 57% deemed inappropriate, and extreme aPTT values were related to prior inappropriate adjustments. The study highlights the need for improved guideline adherence when using this high-risk drug.
Analytical Considerations When Monitoring Pain Medications by LC-MS/MSDavid Masters-Moore
Laboratory urine drug testing of patients on chronic opioid therapy requires providing a large test menu of medications commonly prescribed for this population as well as metabolites and illicit substances. It has been shown that liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred method to analyze urine specimens for these substances.
Purpose of the study: To describe the challenges and some of the techniques to validate the analytical procedures used to identify and quantify these medications and substances.
Methods: Using data obtained from testing over one million specimens, the authors developed a proposed test menu. Potential isobaric interferences were established by using literature references. A list of potentially interfering medications was obtained by using the proposed test menu and the most commonly prescribed medications. Finally, criteria were designed to detect possible carryover.
Results: The LC-MS/MS instrumentation eliminated all potential interferences and provided quantitative data over the test range needed to monitor these patients. Carryover could be eliminated by setting the carryover thresholds for each analyte.
Conclusions: Reference laboratories utilizing LC-MS/MS technology to conduct urine drug testing for pain clinicians should employ specific techniques described in this study to develop an optimal test menu and validate procedures that include isolating retention times for isobaric compounds, identifying interfering substances including impurities in medicinal and illicit substance preparations, monitoring ion suppression, and avoiding carryover.
This study evaluated intensity modulated radiotherapy (IMRT) plans for 10 simulated tracheal tumor patients that accounted for optimization convergence errors (OCEs). Plans optimized without OCE corrections showed significantly more target dose inhomogeneity compared to plans optimized using a method to correct for differences between the optimization and dose calculation algorithms. Correcting for OCEs resulted in IMRT plans with more conformal and homogeneous target dose distributions for intraluminal tracheal tumors.
ICH guidelines provide standards for toxicity studies to ensure safe, effective, and high quality pharmaceutical products. Guideline S3A deals with conducting toxicity studies and quantifying exposure. General principles include quantifying exposure levels in different species and sexes using plasma concentration or area under the curve. Toxicokinetic studies should be performed to determine metabolite levels and justify dose levels. Reporting should include detailed toxicokinetic data and evaluation. Toxicokinetics are assessed in various toxicity studies including single dose studies, repeated dose studies, genotoxicity studies, carcinogenicity studies, and reproductive toxicity studies.
This is the presentation on Role of advancement in instrumentation in pharmacodynamic evaluation of drugs
in clinical trials.
CONTENTS
Concept of medical instrument and instrumentation
Centrifuge
PCR
HPLC
Flow cytometry
Mass SPECTROMETRY
Minimally invasive technologies in PD
Conclusion
This document presents the development and validation of a new RP-UPLC method for the simultaneous estimation of lamivudine, tenofovir, and efavirenz in tablet dosage forms. The optimized method uses a C18 BEH column, a mobile phase of 35% phosphate buffer (pH 3.0) and 65% methanol, and detects the drugs at 260 nm. The method was validated per ICH guidelines and found to be specific, precise, accurate, linear, robust, and stability-indicating for the simultaneous analysis of the drugs without interference from excipients. The developed and validated RP-UPLC method provides a simple, rapid, and economical approach for the routine quality control analysis of fixed
The document describes the development of an enhanced performance test mix for monitoring high-throughput LC/MS systems used in pharmaceutical analysis. The test mix was designed to:
1) Consist of 8 drug-like compounds selected from a pool of 137 compounds to represent typical properties like mass, hydrophobicity, and charge state.
2) Monitor key aspects of LC/MS performance including separation (gradient, flow, pH), detection (UV, ELS, MS signal), and mass accuracy across different conditions.
3) Provide diagnostic information about the likely cause of any errors based on differences observed in test mix results compared to historical data.
Differential spectrophotometric method for estimation and validation of Verap...roshan telrandhe
The aimed of current research to development of the simple, rapid and sensitive Differential spectrophotometric method for the estimation of Verapamil in tablet dosage form. In this method two medium was use acid and alkaline and the difference spectrum was calculated. 0.1N HCL and 0.1N NaOH was used in this differential method. The λmax 278, beeers law limits 525µg/ml, regression equation Y= 0.024x-0.009, slope 0.024, intercept 0.09, correlation coefficient (r2) 0.998, %RSD <1.5, % Recovery (Tablet) 100.46% was shows the good efficacy and results. This method future scope in quality control of the verapamine in simple, precise and economically and it recommended for the routine drug quality analysis investigation.
This document discusses approaches for identifying somatic mutations from cancer sequencing data using multiple mutation callers. It compares several popular mutation callers, explores a simple consensus approach, and proposes an integrated ensemble approach. The ensemble approach applies multiple callers, filters using GATK, and assigns a ranking score to variants based on validation rates to generate a high-confidence list of somatic mutations. This strategy aims to leverage the strengths of different callers to improve accuracy over any single caller.
Therapeutic drug monitoring (TDM) involves measuring drug levels in a patient's blood or plasma to ensure concentrations remain within a therapeutic range. TDM is useful for drugs with a narrow therapeutic window, high individual variability in effects, or when clinical effects are difficult to observe. Factors like dosage, sampling time, drug interactions, and individual physiology can impact drug levels and require monitoring to optimize treatment and avoid toxicity. Common methods to measure drug concentrations include chromatography techniques coupled with mass spectrometry, as well as various immunoassays.
Recent Advances in Respiratory Physiotherapy 2.pptxSaumyaKine
Recent advances in Respiratory physiotherapy covers a comprehensive aspect of newer technologies helpful in the field of pulmonary physiotherapy. Useful for MPT students. Has articles added up for reference.
Prescription event monitoring and record linkage systemRumana Hameed
PEM is a method of pharmacovigilance that studies drug safety in real-world clinical practice. It involves collecting prescription data for new drugs and surveying prescribers about patient outcomes. Advantages include a large national scale and obtaining real-world safety data. Record linkage systems combine different healthcare records to efficiently study relationships between drug exposure and health outcomes. Claims databases contain prescription and medical claims information but may lack clinical details, while medical record databases provide more clinical data but only for illnesses that were medically attended to.
UV Spectrophotometric Method Development and Validation for Quantitative Esti...Sagar Savale
U.V Spectrophotometric method have been widely employed in determination of Curcumin in a mixture or fixed dose combination. For the ternary mixture containing Curcumin, no spectrophotometric method for evaluation has been reported so far. Thus our aim is to develop method for Curcumin estimation in ternary mixture using U.V spectrophotometry.
S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES
S3B: PHARMACOKINETICS: GUIDANCE FOR REPEATED DOSE TISSUE DISTRIBUTION STUDIES
This document describes the development and validation of a new spectrofluorimetric method for the estimation of desvenlafaxine succinate in bulk and pharmaceutical formulations. Key points:
1) The method utilizes the native fluorescence of desvenlafaxine succinate with an excitation wavelength of 274 nm and emission wavelength of 305 nm in pH 6 phosphate buffer.
2) The method was found to be linear over a concentration range of 100-900 ng/ml. Validation studies established the method's accuracy, precision, selectivity, robustness and ruggedness according to ICH guidelines.
3) The developed method was successfully applied to the analysis of desvenlafaxine succinate in commercial extended-
This document summarizes a study comparing traditional immunoassay screening followed by confirmation using solid phase extraction and gas chromatography/mass spectrometry (SPE/GC-MS) or liquid chromatography/tandem mass spectrometry (LC-MS/MS) to a new method using automated solid phase extraction coupled to high performance liquid chromatography and tandem mass spectrometry (SPE/HPLC/MS/MS) for analyzing urine samples submitted for driving under the influence (DUI) cases. In the study, 106 samples previously confirmed positive by the traditional methods were re-analyzed using the new automated SPE/HPLC/MS/MS method. The new method found additional positive results for THC, amphetamines, benzodiazep
This document summarizes a study comparing traditional immunoassay screening followed by confirmation using solid phase extraction and gas chromatography/mass spectrometry (SPE/GC-MS) versus automated solid phase extraction high performance liquid chromatography tandem mass spectrometry (SPE/HPLC/MS/MS) for analyzing urine samples submitted for driving under the influence (DUI) cases. 106 samples previously confirmed positive by the traditional methods were re-analyzed using the automated SPE/HPLC/MS/MS system. More drugs were detected using the automated system, including 12 additional THC cases, 4 additional amphetamine cases, 6 additional benzodiazepine cases, and 3 additional cocaine cases. The automated system was able to process samples faster and at
Automated Chromatographic Solid-Phase Extraction Using an Autosampler _ Ameri...Rick Youngblood
1) Automated solid-phase extraction (SPE) using an autosampler increases sample throughput compared to manual SPE. An autosampler transports micro SPE cartridges containing chromatographic media and performs conditioning, loading, washing, and elution steps directly on an LC/MS or GC/MS system.
2) Precise syringe pump flow control over the packed sorbent bed in micro SPE cartridges enables optimal separations. This results in systematically high and precise analyte recoveries not typically achieved with other SPE methods.
3) Integrating SPE directly into LC/MS or GC/MS analysis as an online workflow using an autosampler achieves higher quality results than a two-step robotic process
This document provides an intermediate course for lab personnel on using an ITSP PAL autosampler. It discusses (1) using PAL Loader software to manage firmware, (2) using PAL Object Manager software to manage objects, (3) using the local terminal to manage objects and positions, (4) important ITSP concepts, and (5) regular maintenance procedures. The document includes screenshots and step-by-step instructions for processes like teaching positions, verifying positions, and troubleshooting firmware issues.
This document provides an overview of an advanced training course for ITSP PAL Method developers. The course covers topics like using Cycle Composer software to create and edit macros and methods, converting macros to cycles, important ITSP concepts, and reviewing control levels, sample lists, methods, macros, atoms, and firmware. It includes examples of macro code and discusses best practices for developing macros, variables, synchronization, and exercises for attendees to practice these skills. The intended audience is experienced ITSP lab personnel looking to develop new methods and macros for the ITSP PAL system.
This document provides an overview of an ITSP PAL Basic Course for lab personnel. The course covers using the local terminal on the PAL to maintain it, using software to manage methods and sample lists, and important ITSP concepts. Topics include an overview of ITSP, the PAL terminal, software for method and sample list management, important concepts, and hardware components like cartridges and accessories. The course is intended to familiarize lab staff with operating an ITSP PAL system.
This document proposes modifications to an existing dual rail autosampler to implement a fully automated opiates method using ITSP SPE cartridges. The key points are:
1) Hardware modifications include adding ITSP tray holders, SPE solvent stations, and modifying a needle guide to interface with the ITSP cartridges.
2) Software modifications involve adding objects to support the new hardware and direct synchronization between rails to overlap operations and improve throughput.
3) The proposed method uses ITSP SPE cartridges to concentrate and purify samples prior to injection, which improves chromatography, reduces maintenance, and allows for automated sample preparation.
This document describes a new technology called Instrument Top Sample Prep (ITSP) that automates solid phase extraction (SPE) directly on the autosampler of a gas chromatograph. ITSP uses proprietary cartridges that can be manipulated by the autosampler to perform SPE in a cost-effective manner without the need for additional expensive equipment. The autosampler syringe acts as the solvent reservoir, allowing SPE to be conducted in a miniaturized and automated fashion. ITSP cartridges integrate SPE into the workflow of analytical instruments to increase efficiency and productivity of sample preparation and analysis.
This document describes the development of an automated online SPE-LC/MS/MS method for pain management drug monitoring. Key aspects include:
1) A single method was developed to measure all relevant pain management drugs, including opioids and benzodiazepines, in a simplified workflow.
2) Method optimization focused on achieving high recovery for the lowest prescribed drug levels.
3) The method uses serial automated SPE on an LC autosampler to enable a total cycle time of 4.5 minutes for SPE and LC/MS/MS analysis.
4) Automated SPE method development was efficient, requiring only 3 lab days to optimize using a single SPE-LC/MS/MS system.
This document describes the development of an automated SPE-LC/MS/MS method for the simultaneous measurement of multiple drugs of abuse in urine and oral fluid samples. Key points:
- An online SPE method was optimized on an autosampler to pre-concentrate samples prior to LC/MS/MS analysis, allowing all drugs to be measured in a single run.
- Method development focused on optimizing recoveries for the lowest dose and hardest to measure drugs. Automation facilitated rapid testing and transfer of optimized parameters between steps.
- The method demonstrated linear response over a 100-500 μL sample loading range and achieved a total analysis time of 4.5 minutes per sample for SPE and LC/MS/
This document provides instructions and details for setting up an ITSP (Instrument Top Sample Prep) system on a PAL autosampler. ITSP uses disposable cartridges containing chromatographic media that are manipulated by the autosampler to automate sample cleanup and preparation. The document discusses required accessories like cartridge trays and waste stations and provides tips for proper training of reference positions. It also explains how the ITSP system performs solid phase extraction in a fully automated manner using the autosampler syringe to control flow rates.
This presentation introduces ITSP (Instrument Top Sample Prep) which is a consumable solution for automating solid phase extraction (SPE) sample cleanup directly on the autosampler of analytical instruments like LC-MSMS and GC-MS. ITSP uses patented cartridges containing user-defined SPE media that are transported by the autosampler to facilitate just-in-time filtration and extraction of samples prior to analysis. ITSP provides benefits like improved chromatography, increased throughput, and reduced solvent usage and costs compared to traditional batch sample preparation methods. The system works with various autosamplers and markets including clinical, environmental, food safety, and pharmaceutical applications.
An automated method was developed to extract and analyze barbiturates and THCA from human urine using ITSP solid phase extraction and liquid chromatography-mass spectrometry. Standards of six barbiturates and THCA were prepared in urine over ranges of 0.1-20 μg/mL and 0.01-2.0 μg/mL respectively and processed using an ITSP cleanup followed by LC-MS/MS analysis. Linear calibration curves were obtained for all analytes with R2 values greater than 0.99, demonstrating the method is suitable for quantifying the target compounds in urine.
This document describes a method for automating the analysis of androstenedione and testosterone in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Key aspects of the method include automated protein precipitation, solid phase extraction cleanup, LC-MS/MS analysis, and fully integrated control via software. Calibration curves for androstenedione and testosterone showed good linearity and quality control samples were within specified ranges, validating the method. The automated system is capable of handling 98 samples in under 14 hours.
This document compares the efficiency of using automated solid phase extraction coupled with high performance liquid chromatography and tandem mass spectrometry (SPE-HPLC/MS/MS) versus traditional immunoassay screening followed by SPE-GC/MS or SPE-LC/MS/MS confirmation for analyzing postmortem blood samples submitted in death investigation cases. The study finds that automated SPE-HPLC/MS/MS using an Instrument Top Sample Preparation (ITSP) system provides results generally in agreement with traditional methods, with improved efficiency through integrated online sample preparation and reduced analysis time and costs. The automated method was able to extract and analyze samples stored for up to 12 months, demonstrating its robustness for difficult biological matrices.
ITSP Solutions challenges readers to develop a proof of concept application using simple extraction tools that reduces solvent volumes to less than an autosampler vial. If successful, ITSP Solutions will develop macros from the method and transfer them to a PAL System for a live demo. If a PAL System is then purchased, ITSP Solutions will provide the hardware kit for free.
This document describes the development and validation of an LC-MS/MS method for analyzing streptomycin and dihydrostreptomycin residues in honey. Various HILIC columns were tested and a ZIC-cHILIC column provided the best separation of the two compounds. An ITSP clean-up step using weak cation exchange SPE removed sugars from honey extracts to reduce ion suppression. The method was validated according to EU guidelines, with mean recoveries of 98-105% and method detection limits below the regulatory limits of 0.02-0.05 mg/kg.
Automated SPE for Capillary Microsampling PosterRick Youngblood
1) An automated SPE method using small single-use cartridges was evaluated for plasma samples derived from capillary microsampling as an alternative to manual protein precipitation.
2) Results from the automated SPE method were comparable to manual protein precipitation in terms of accuracy, precision, calibration curves, and limits of quantification. The automated method provided equivalent results but with less hands-on time.
3) Further optimization is possible, including reducing the plasma sample volume and elution volume to allow analysis of samples from microsampling techniques using minimal volumes.
This document describes a fully automated method for analyzing NDMA (N-Nitrosodimethylamine) levels in water samples. NDMA is a carcinogen found in some drinking water sources at low concentrations. The method uses solid phase extraction cartridges containing coconut charcoal to enrich NDMA from water samples. The extraction process and injection onto a gas chromatograph/mass spectrometer for analysis are both automated using a multipurpose sampler. Recoveries of NDMA from spiked water samples using this automated method averaged 110% compared to reference standards, demonstrating the method's accuracy for quantifying NDMA levels in water.
This document discusses eliminating the need for matrix-matched calibration standards for pesticide residue analysis of QuEChERS extracts using an automated solid phase extraction cleanup procedure. It finds that an Instrument Top Sample Preparation (ITSP) robotic SPE cleanup using Z-Sep/C-18/CarbonX cartridges more effectively removes non-polar matrix like oils from complex samples compared to dispersive SPE. This improved matrix removal allows the use of solvent-only calibration standards and obtains acceptable recoveries for most pesticides tested, especially for analyses of spices, food ingredients, kiwifruit, and marigold oleoresin extracts.
This document discusses ITSP (The MicroLiter Plate Sampling System), a technology that can increase lab productivity and reduce solvent usage. ITSP allows labs to prepare samples using solid-phase extraction or filtration using their existing autosampler, such as a CTC Analytics PAL. ITSP can help labs reduce capital expenses, help the environment by lowering solvent usage by up to 70%, and potentially justify converting sample preparation methods. The company offers to provide labs with ITSP devices to develop methods which can then be automated, and will partner with CTC PAL resellers to configure systems for those without a PAL.
1. PainManagement&
DrugsofAbuse
MeasuredinUrine
and/orOralFluid
Measuring all the drugs at
all the relevant concentrations in a
single unified method / workflow using
an ITSP solution for on-line
SPE-LC/MS/MS
Developed in collaboration with
Assurance Scientific Laboratories
Instrument Top Sample Prep
Aconsumablesolutionforautomationand
thebestmeasurementperformance!
71+Drugs, 4.5 MinutesInject-to-Inject,
Two 96-position traysperinstrumentovernight
5. Mobile Phases:
A–TraceanalyticalgradewaterfreshfromaMilliporeIntegral
WaterPurificationSystemw/BioPak(orequivalent)buffered
with1%HOAc(atomicanalysisgrade,Flukaproduct
no.:07692)
B–ACN(LC/MSgrade,Honeywellproductno.:015-4)
Column:
GLSciencesInertsilC18 ODS3,3µmparticles,2.1x50mmorsame
sizebiphenylcolumn(RestekRaptor)heldat50°Cusingaheat
exchangerincolumnoventopreheatmobilephase.
Gradient (1 ml/min):
Time= 0.00: 97%A,3%B(start)
Time= 0.05: 97%A,3%B(hold)
Time= 0.60: 80%A,20%B(lineargradient)
Time= 3.00: 40%A,60%B(lineargradient)
Time= 3.20: 5%A,95%B(lineargradient)
Time= 3.35: 5%A,95%B(hold)
Time= 3.36: 100%B(columncleanup)
Time= 3.50: 100%B(columncleanup)
Time= 3.51: 97%A,3%B(columnconditioning)
Time= 4.00: 97%A,3%B(columnconditioning)
Dependingonthedrugsmeasured,gradienttransitionpointsand/
orrampratesmayhavetobeadjustedtoseparateisobaricdrugs
and/ortoachieveatleast16datapointsacrosseachLCpeak.
These(andallLC/MS/MSparameters)shouldbeoptimized,fully
functional,andmaderoutinebasedonsolvent/standards-only
solutionspriortoproceedingwithon-lineSPEwithITSP.
LC/MS/MSconditions tocoverawide range ofdrugsafterITSP RP/SPE
Sample Injection by PAL System Relative to
Mass Spec Sensititvity
1)Fillvalve/loopwithtraceanalyticalgradewaterprior
toinjection.
2)Inallcases,apre-cutandpolishedSSloopisused.
3)UsingordinaryLC/MS/MSs: 5μlloopusing>3xoverfill.
Ifpeakshapeand/orretentionareinsufficientforearly
elutingpeaks,checkbufferinginSPEeluent(seeFigure4
below).
4)Usingtop-endLC/MS/MSs: 1-2μlloopusing>3xoverfill
(usenarrowerLCpeakstoimprovespeedand/or
separation).
5)Injectionvolumeshouldbeheldtoamaximumof5μl
whenusinga2.1mmdiameterLCcolumn. Largervolumes
increasepeakareaprimarilyinwidth,notheight,andthus
deterioratetheLCseparationwithlittle,ifany,gainin
sensitivity. AlwaysoperateLC/MS/MSatoptimalconditions.
6) Chemical presentation of the sample from ITSP SPE to
the LC is important. In LC analysis, control of the pH
(ionization state) controls peak shape (see Figure 4).
Elution in 80% ACN limits LC injection volume to ~2µL
(2.1 x 50mm column). Elution in 100% MeOH (buffered)
allows 5µL LC injection. Viscosity has an equally impor-
tant role in LC injection along with pH.
MS/MS Conditions:
UsealltheusualMRMsforalldrugs. BarbituratesandTHCAuse
(–)ionMRMs(Figure5),allothers(+)ion.
Figure 4: This chromatogram illustrates two ITSP SPE elutions, one using
a buffer and the second without.
Pentobarbital
Secobarbital
THCA
Figure 5: This chromatogram illustrates that YES, acidic drugs can be
measured by LC conditions used for basic drugs.