Determination Of Log P For Compounds Of Different Polarity-Books Pdf

Determination of Log P for Compounds of Different Polarity
24 May 2020 | 24 views | 0 downloads | 6 Pages | 996.16 KB

Share Pdf : Determination Of Log P For Compounds Of Different Polarity

Download and Preview : Determination Of Log P For Compounds Of Different Polarity


Report CopyRight/DMCA Form For : Determination Of Log P For Compounds Of Different Polarity



Transcription

Introduction Experimental Compounds analyzed, The distribution of a drug between water The following instruments were used Testosterone 48 mg 10 mL. and octanol is one criterion to determine Pindolol 36 7 mg 10 mL. how lipophilic the compound is The Agilent 1200 Infinity Series Ibuprofen 78 5 mg 10 mL and. distribution coefficient log P gives HDR DAD Impurity Analyzer Paracetamol 79 mg 10 mL purchased. an indication of how easily the drug is System from Sigma Aldrich Germany. adsorbed how strong the effect is how, long it remains in the body in an active Agilent 1290 Infinity DAD with. form and how it is metabolized and 60 mm cell G4212A H. The partition coefficient is a ratio of Agilent 1290 Infinity DAD with HO. concentrations of unionized compound 3 7 mm cell G4212A Paracetamol Testosterone. between the two solutions To measure, the partition coefficient of ionizable Agilent High Dynamic Range DAD H. solutes the pH of the aqueous phase Solution Kit G2199AA. is adjusted such that the predominant CH3, form of the compound is unionized Agilent 1290 Infinity Thermostated H. The logarithm of the ratio of the Column Compartment G1316C Pindolol Ibuprofen. concentrations of the unionized solute,in the solvents is called log P The log P.
Agilent 1290 Infinity Autosampler,value is also known as a measure of. lipophilicity1 The distribution coefficient G4226A. for ionizable compounds depends on, the pH The pharmaceutical industry Agilent 1290 Infinity Thermostat. measures the log P value at pH 7 4 G1330B,This is the physiological pH of blood. serum2 The equation typically used is Agilent 1290 Infinity Quaternary. Pump G4204A,log P7 4 octanol water log concentrationoctanol. concentration water at pH 7 4,Chromatographic conditions.
The EPA guidelines3 give a, recommendation on how to perform a Parameter Value. log P calculation using HPLC Column Agilent ZORBAX RRHD Eclipse Plus C18 4 6 50 mm 3 5 m p n 959943 902. Flow rate 1 mL min,One problem using the HPLC approach. Mobile phases A Water,is that one phase might contain. B Acetonitrile,approximately the complete amount of C 1 TFA. the dissolved drug whereas the other, Gradient at 0 minutes 5 B 10 C at 8 minutes 90 B 10 C.
phase only contains traces In this case it, is advantageous that the HPLC detection Run time 10 minutes. system provide a wide linear range Post time 3 minutes. and also high sensitivity The Agilent Temperature 30 C. 1200 Infinity Series HDR DAD Impurity Detection 230 10 nm Ref off 20 Hz. Analyzer System fulfilled both demands Injection volume 1 L. Typically the linear range goes up to,6 000 mAU and peaks below 0 5 mAU are. detectable4,This Application Note shows that the,log P values of compounds with different. lipophilicity were determined using the,1200 Infinity Series HDR DAD Impurity. Analyzer System,Sample preparation Calibration concentrations.
1 The water phase was adjusted to Paracetamol Ibuprofen Pindolol Testosterone. pH 7 4 with phosphate buffer and g mL g mL g mL g mL. saturated with octanol Stock 7 700 7 850 3 670 13 663. 2 The octanol phase was saturated Dilution 1 3 850 3 925 1 835 2 732 6. with water Dilution 2 1 540 1 570 734 546 52,Dilution 3 308 314 146 8 109 304. 3 Both phases were left for separation,for 24 hours Dilution 4 61 6 62 8 29 36 21 8608. Dilution 5 12 32 12 56 5 872 4 37216,4 Compounds were weighed and. dissolved in 10 mL of water at pH 7 4 Dilution 6 2 464 2 512 1 1744 0 874432. and octanol 50 50,5 The phases were shaken and left for. separation for 24 hours,6 A solution of 1 mL of the water.
and 1 mL of the octanol phase was,transferred into a 1 5 mL vial and. Acquisition and evaluation,Agilent OpenLAB CDS ChemStation. Rev C 01 05,Results and Discussion,The 1200 Infinity Series HDR DAD. Impurity Analyzer System was configured,during instrument configuration Both. detectors were clustered The delay,volume of the capillary connecting both.
detectors was determined and filled,in the configuration table In the user. interface both detectors appear as one,detector Figure 1. The following experiments were done to,determine log P. Calibration tables were generated,to determine the linearity range. and sensitivity of the method detectors, The water and octanol phase Figure 1 User interface in the Agilent ChemStation.
were analyzed to determine the,concentrations in both phases. for testosterone paracetamol,ibuprofen and pindolol. Log P was calculated, Linearity and Limit of mAU Calibration level 6 at detection limit. Detection LOD 30,Linearity was measured using calibration 25. standards from the stock solution down,Stock solution up to peak heights of 8 000 mAU 20.
to level 6 The stock solution was the mAU,Paracetamol. highest concentration and level 6 was Testosterone 15. the lowest concentration Figure 2 The,stock solution resulted in peak heights. of approximately 8 000 mAU The lowest 5 000 5, calibration level was close to the LOD 4 000 2 3 4 5 6 min. with peak heights smaller than 1 mAU 3 000,2 000 Pindolol. The 1200 Infinity Series HDR DAD 1 000,typically provides a 30 times enhanced 0.
linear range compared to conventional 2 3 4 5 6 7 min. DADs4 The calibration curves Figure 3,The highest calibration level represents. provided sufficient linearity for all,Paracetamol 7 700 ng injected amount. compounds Pindolol 3 670 ng injected amount,Ibuprofen 7 850 ng injected amount. Testosterone 13 663 ng injected amount,The lowest calibration level represents. Paracetamol 2 5 ng injected amount,Pindolol 1 3 ng injected amount.
Ibuprofen 2 5 ng injected amount,Testosterone 0 874 ng injected amount. Figure 2 Chromatogram of highest and lowest calibration concentration of paracetamol pindolol. testosterone and ibuprofen,Area Ibuprofen DAD1 A Area Paracetamol DAD1 A. 8 000 Area 1 03175717 Amt 30 329114 20 000 Area 2 63116408 Amt 113 50861. 7 000 Rel Res 1 94 403 17 500 Rel Res 3 36 911,6 000 15 000. 5 000 12 500,4 000 10 000,3 000 7 500,2 000 5 000, 1 000 Correlation 0 99979 2 500 Correlation 0 99943. 0 2 000 4 000 6 000 Amount g mL 0 2 000 4 000 6 000 Amount g mL. Area Pindolol DAD1 A Area Testosterone DAD1 A, Area 1 25629334 Amt 28 352578 Area 1 76855043 Amt 109 27699.
4 000 Rel Res 2 75 942 Rel Res 7 98 282,3 000 15 000. 2 000 10 000,1 000 5 000,Correlation 0 99953 Correlation 0 99958. 0 1 000 2 000 3 000 Amount g mL 0 5 000 10 000 Amount g mL. Figure 3 Calibration curves,Analysis of the water and mAU mAU. Testosterone,octanol phase,Testosterone is a compound which. is almost nonsoluble in water 500,Consequently the peak in the water 30.
Testosterone,phase was very low Figure 4 Whereas,the testosterone peak in the octanol 300 25. phase was approximately 700 mAU high,the peak in the water phase was only 200. 0 41 mAU high 20 Peak height 0 41 mAU 0 66 g mL,Paracetamol showed nearly equal. distribution between water and octanol 15, Pindolol dissolved slightly better in water 1 0 1 2 3 4 5 6 7 min 5 1 5 2 5 3 5 4 5 5 5 6 5 7 5 8 5 9 6 0 min. and ibuprofen dissolved significantly, better in octanol Figure 5 The peak Figure 4 Analysis of testosterone in the octanol and water phase.
heights for ibuprofen and paracetamol,were 2 500 and 4 500 mAU far beyond. the linear range of a conventional DAD,Using the 1200 Infinity Series HDR DAD. quantitation was possible with reliable,results even for these high concentration. Paracetamol 1 200 Pindolol Ibuprofen,2 500 1 500, 1 1 2 1 4 1 6 1 8 2 2 2 2 4 min 2 2 25 2 5 2 75 3 3 25 3 5 3 75 4 min 6 6 2 6 4 6 6 6 8 7 min. Figure 5 Distribution between water blue and octanol red for pindolol ibuprofen and paracetamol. Calculation of log P Table 1 Calculation of log P, The log P values were calculated based Concentration Log P at.
on the evaluated concentration in the octanol Concentration water Partition Log P at pH 7 4 from. water and octanol phase Except for Compound g mL at pH 7 4 g mL coefficient pH 7 4 literature. paracetamol the calculated values Ibuprofen 7 327 75 391 79 18 703 1 27 1 37. showed good correlations with data from Testosterone 1 259 39 0 66 1 920 098 3 28 3 29. the literature5 Table 1 Paracetamol 3 775 25 2 918 93 1 293 0 11 0 51. Pindolol 1 575 73 3 008 82 0 524 0 28 0 21,Conclusion. Determination of log P was done using,the Agilent 1200 Infinity Series HDR DAD. Impurity Analyzer System Quantitation References 4 Huesgen A G Comparison of. of significantly different concentration sensitivity and linearity of the Agilent. levels present in the water and the 1 Wikipedia Partition Coefficient. 1200 Infinity Series high Dynamic, octanol phase were performed without http en wikipedia org wiki. Range Diode Array Detector Solution, the need of injection volume adaption Partition coefficient accessed. and the conventional Agilent 1290, Peak heights up to 8 000 mAU were February 10th 2014.
Infinity DAD Agilent Technologies, calibrated and quantified due to the wide Application Note publication number. 2 Cairns D Essentials of, linear range of the 1200 Infinity Series 5991 1890EN 2013. Pharmaceutical Chemistry 4th Edition,HDR DAD Conversely peaks as low as. 2012 Jan ISBN 978 0 85369 979 8, 0 41 mAU were quantified due to the low 5 Kerns E H et al Pharmaceutical. Chapter 3 p 60, noise behavior of the 1200 Infinity Series profiling method for lipophilicity and.
HDR DAD 3 United States Environmental integrity using liquid chromatography. Protection Agency Prevention mass spectrometry Journal of. Pesticides and Toxic Substances Chromatography B 2003 791 381 388. 7101 EPA 712 C 96 038 August,www agilent com chem, This information is subject to change without notice. Agilent Technologies Inc 2014 2019,Published in the USA January 8 2019. The determination of log P the distribution of a compound between water and octanol is frequently used in the pharmaceutical industry to evaluate the lipophilicity of a compound Especially if the distribution between the water and the octanol phase is significantly different the linear range of the detector must be extremely wide or the applied injection volumes have to be adjusted

Related Books

Analisis Wacana artikel De Charlie a Charlie dalam surat

Analisis Wacana artikel De Charlie a Charlie dalam surat

DALAM SURAT KABAR LE MONDE Skripsi Diajukan kepada Fakultas Bahasa dan Seni Univeritas Negeri Yogyakarta Untuk memenuhi sebagian persyaratan guna memperoleh gelar Sarjana Pendidikan Oleh Lina Listyari Kusumaningrum 12204247002 PROGRAM STUDI PENDIDIKAN BAHASA PRANCIS FAKULTAS BAHASA DAN SENI UNIVERSITAS NEGERI YOGYAKARTA 2016 ii KEMENTERIAN RISET TEKNOLOGI DAN PENDIDIKAN TINGGI

188

188

DAPTAR PUSTAKA A Jurnal Ilmiah Adhayato Oksep 2011 Khilafah Dalam sistem Pemerintahan Islam Jurnal Ilmu Politik dan Ilmu Pemerintahan Vol 1 No 1 Pp 80 98 Afandi Rifki 2011 Integrasi Pendidikan Karakter Dalam Pembelajaran IPS di Sekolah Dasar Pedagogia Vol 1 No 1 Pp 85 98 Amelia Lia jeung Een Herdiani 2007 Peran dan Citra Perempuan dalam Tari Sunda

2008 Chevrolet Silverado Owner Manual M General Motors

2008 Chevrolet Silverado Owner Manual M General Motors

Vehicle Damage Warnings Notices are also used in this manual Notice These mean there is something that could damage your vehicle A notice tells about something that can damage the vehicle

Getting to Know Your 2008 Malibu Chevrolet

Getting to Know Your 2008 Malibu Chevrolet

Getting to Know Your 2008 Malibu Congratulations on your purchase of a Chevrolet Malibu Please read this information about your vehicle s features and your Owner Manual to ensure an outstanding ownership experience Note that your vehicle may not include all the features described in this booklet Keep this booklet with your Owner Manual for

Medical Surge Capacity and Capability

Medical Surge Capacity and Capability

Medical Surge Capacity and Capability Executive Summary health centers private physician offices and others as noted on page 2 2 Thus each healthcare asset must have information management processes to enable integration among HCOs at Tier 2 and with higher management tiers Management of a Healthcare Coalition Tier 2 Coordination among local healthcare assets is critical to

The Capability Approach and Human Development Some

The Capability Approach and Human Development Some

the capability approach concedes too much ground to the demands of individualism to the relative neglect of society The second part seeks to clarify a number of inter related issues concerning choice and freedom the two most fundamental concepts in the capability approach Finally I make some concluding observations and offer some suggestions on how the human development discourse might

Resource Based View of the Firm and Innovation

Resource Based View of the Firm and Innovation

The Resource Based View of the Firm and Innovation Identification of Critical Linkages Konstantinos C Kostopoulos Doctoral Candidate Management Sciences Laboratory Athens University of Economics and Business 47A Evelpidon amp 33 Lefkados GR 113 62 Athens Greece axion aueb gr Yiannis E Spanos

Best Practices in Capacity Building Approaches OpenEI org

Best Practices in Capacity Building Approaches OpenEI org

Best Practices in Capacity Building Approaches Recommendations for the Design of a Long Term Capacity Building Strategy for the Wind and Solar Sectors by the MEF Working Group Deutsche Gesellschaft f r Technische Zusammenarbeit GTZ GmbH Contact Joscha Rosenbusch Potsdamer Platz 10 10785 Berlin E joscha rosenbusch gtz de Author Ilka N Buss Frankfurt December 2010 Abbreviations AEEP

Defense Resource Management Studies Introduction to

Defense Resource Management Studies Introduction to

Defense Resource Management Studies Introduction to Capability and Acquisition Planning Processes Mark E Tillman Alfred H Gollwitzer Gregory H Parlier Charles V Fletcher Project Leader Wade P Hinkle Project Leader Log H 10 000858 Approved for public release distribution is unlimited About This Publication This work was conducted by the Institute for Defense Analyses IDA under

Comparison of Installed Capacity ICAP amp Unforced

Comparison of Installed Capacity ICAP amp Unforced

Installed Capacity ICAP A MW value based on the summer net dependable capability of a unit and within the capacity interconnection right limits of the bus to which it is connected Unforced Capacity UCAP The MW value of a capacity resource in the PJM Capacity Market For a generating unit the unforced capacity value is equal to the

Analyzing Resources and Capabilities

Analyzing Resources and Capabilities

l Putting Resource and Capability Analysis to Work A Practical Guide Step 1 Identify the Key Resources and Capabilities CSAC05 1 13 07 9 21 Page 123 124 PART II THE TOOLS OF STRATEGY ANALYSIS Introduction and Objectives In Chapter 1 I noted that the focus of strategy thinking has been shifted from the exter nal environment towards its internal environment In this chapter we will make the