pharmaceutical impurity analysis solutions - Lcms-connect.com

More documents

Recommendations

Info

Liquid Chromatography andUltraviolet Spectrometry(LC/UV)Agilent 1200 Infi nity Series LC Systems and columnsA number of impurity analysis methods found in pharmaceutical quality control(QC) laboratories use high-performance liquid chromatography (HPLC) coupledwith UV detection (HPLC/UV methods). UV spectrometry helps identify impurity ordegradants in drug substances based on absorption maxima. This technique is oneof the most important and versatile analytical methods available for impurity profi lingtoday due to its high selectivity (i.e., ability to quantitatively determine a number ofthe individual components present in a sample using a single analytical procedure),especially for routine analysis where standards are available. Newer, stationaryphase systems are available which operate in several modes, such as ion pairing,increased hydrophobic interactions, and variable pH, allowing a variety of samplesto be analyzed concurrently based upon their unique properties. High resolution isparticularly helpful when using LC/UV analysis for impurity detection, because allimpurities can be identifi ed with less chance of error. Figure 2 demonstrates theresults achieved using an Agilent LC system combined with Agilent 1.8 μm RRHDcolumns identifying and quantifying seven impurities.Isocratic Impurity MethodColumn: 4.6 x 150 mm, 5 µmmAU2.521.510.50-0.5-10 5 10 15 20 min4.6 x 150, 5 µmRs = 1.15G/N = 424.6 x 150, 3.5 µmRs = 1.37S/N = 504.6 x 150, 1.8 µmRs = 1.80 (+57 %)S/N = 444 impurities baselinenot separated for 27 impurities baselinenot separated for 67 impurities baselineseparated for allFigure 2. This data demonstrates the value of UHPLC systems, like the Agilent 1290/1260/1220 InfinitySeries systems, for impurity analysis. When combined with Agilent 1.8 μm RRHD columns, it waspossible to identify all seven impurities with good baseline separation for accurate quantification. AgilentTechnologies, unpublished data.10
Liquid Chromatography andMass Spectrometry (LC/MS)6100 Series Single Quad 6500 Series Q-TOF6400 Series Triple QuadAgilent Mass SpectrometersLC/MS is a powerful analytical tool that is routinely used in pharmaceuticaldevelopment to test and identify product impurities. The detection limit of a fewhundred ppm is readily achievable, ensuring the identifi cation of all the impuritiespresent at concentrations greater than 0.1 %. MS-based methods generally provideadditional robustness and ruggedness compared to techniques such as UV alone, dueto their high specifi city and sensitivity. While single quadrupole mass spectrometerswork well as analytical tools for the confi rmation of known impurities and thepreliminary structural assessment of unknown impurities, highly sensitive Q-TOFmass spectrometers provide higher resolution and mass accuracy that enables theunambiguous identifi cation of unknown trace impurities, making them very useful forgenotoxic impurity analysis. MS-based methods are often selected for the impurityprofi ling of APIs during process development, while UV-based methods are generallyused to test for genotoxic impurities in QC laboratories at manufacturing sites.Triple-quadrupole (QQQ) LC/MS/MS systems have become a standard platformfor the quantitative analysis of organic impurities in pharmaceutical analyticallaboratories. Combining multiple reaction monitoring (MRM) with a triplequadrupole tandem mass spectrometer, such as the Agilent 6400 Series QQQ,enables extraordinary sensitivity for multi-analyte quantitative assays. MRM assaysare particularly useful for the targeted analysis of compounds present in complexmixtures and matrices, such as blood.Capillary Electrophoresis (CE)Agilent 7100 CE instrumentThe determination of drug-related impurities is currently the most important task forCE within pharmaceutical analysis because it achieves high separation effi cienciescompared to other chromatographic techniques. CE can be employed whenHPLC techniques are not able to adequately measure impurities, especially in thecase of very polar compounds. A detection limit of 0.1 % is widely accepted as aminimum requirement for a related impurities determination method and this can beachieved using CE. In addition, CE is very useful for the separation of closely relatedcompounds, such as diastereomers and enantiomers. An example of the value of CEin impurity analysis can be demonstrated using heparin (a polymeric anticoagulant)as an example. In this case, standard chromatography failed to distinguish drug lotsassociated with adverse events while CE was easily able to identify an unknownimpurity (Figure 3). As a result, the use of CE helped to solve this analytical challenge.mAU605040302010024 6 8 minFigure 3. Capillary electrophoresis of heparin and related impurities using highly concentrated buffers in a25μm bubble cell capillary. See Agilent publication 5990-3517EN.11
Page 1: PHARMACEUTICAL IMPURITYANALYSIS SOL
Page 4 and 5: 1PHARMACEUTICAL IMPURITY ANALYSIS -
Page 6 and 7: should be avoided. Class II solvent
Page 8 and 9: 2ANALYTICAL TECHNOLOGIES FOR IMPURI
Page 12 and 13: Supercritical FluidChromatography (
Page 14 and 15: Gas Chromatography (GC)7890A/5975C
Page 16 and 17: 3.1ANALYSIS OF ORGANIC IMPURITIESAc
Page 18 and 19: The advantage of using ISET’s sea
Page 20 and 21: Improve profiling productivityfor t
Page 22 and 23: AmAU40Chlorhexidine, spiked with 1
Page 24 and 25: 3.2ANALYSIS OF INORGANIC IMPURITIES
Page 26 and 27: 3.3RESIDUAL SOLVENT ANALYSISFaster
Page 28 and 29: Agilent Residual SolventAnalysis Pu
Page 32: Learn morewww.agilent.com/lifescien

pharmaceutical impurity analysis solutions - Lcms-connect.com

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?