WIXLIB

18826Column: Kinetex Core-Shell C18 2.6 µm1Dimensions: 100 x 4.6 mmPart No.: 00D-4462-E0Flow Rate: 0.6 mL/min3Sample: 1. Impurity B2. Impurity A3. Impurity J4. Impurity I5. Impurities D and E6. Impurity F7. Impurity G8. Impurity H24Rs Impurities I and J: 2.36024681018827875121416App ID 18826Elution Time of Last Peak: 20.0 min1820minMethod 3Even Faster and Higher Resolution within Allowable AdjustmentsColumn: Kinetex Core-Shell C18 2.6 µmDimensions: 100 x 4.6 mm1Part No.: 00D-4462-E0Flow Rate: 0.9 mL/min3Sample: 1. Impurity B2. Impurity A3. Impurity J4. Impurity I5. Impurities D and E6. Impurity F7. Impurity G8. Impurity H246Rs Impurities I and J: 3.7250246App ID 18827Elution Time of Last Peak: 11.9 min781081214minAdjustments for Meeting System Suitability(European Pharmacopeia 9.0, Chapter 2.2.46. Chromatographic separation techniques)Allowed AdjustmentsMethod Parameter(isocratic elution)Method 1Method 2Method 3Mobile Phase pH 0.2 units3 (as specified)As specifiedAs specifiedConcentration of Salts inBuffer 10 %As specified in Monograph0703 Details TableAs specifiedAs specifiedComposition of the MobilePhase 30 % of the minor solvent component relative or 2 % absolute, whichever is the larger. No other component isaltered by more than 10 % absolute.As specified in Monograph0703 Details TableAs specifiedAs specifiedWavelength of DetectorNo deviations permitted226 nm (as specified)As specifiedAs specifiedInjection VolumeMay be decreased, provided detectionand repeatability of the peak(s) to bedetermined are satisfactory.10 µL (as specified)As specifiedAs specifiedColumn Temperature 10 CAmbient (as specified)As specifiedAs specifiedStationary PhaseNo change of the identity of thesubstituent permitted (e.g. no replacement of C18 by C8)End-capped octadecylsilylsilica gel for chromatography(as specified)As specifiedAs specifiedColumn Length 70 %125 mm (as specified)100 mm (-20 %)100 mm (-20 %)Column Internal Diameter 25 %4.0 mm (as specified)4.6 mm ( 15 %)4.6 mm ( 15 %)Particle Size-50 %5 µm (as specified)2.6 µm (-48 %)2.6 µm (-48 %)Flow Rate 50 %0.6 mL/min (as specified)As specified0.9 mL/min ( 50 %)PhenomenexlWEB: www.phenomenex.comEuropean Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsMethod 2Faster and Higher Resolution Within Allowable AdjustmentsReduce run time by 10 min9

European Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsCarvediloland Related SubstancesPh. Eur. monograph 1745The Ph. Eur. Monograph 1745 outlines the separation of Carvedilol from impurities. This method wasstudied and improvements were made to provide faster separations within allowable adjustments.CarvedilolPh. Eur. Monograph 1745 DetailsReference Solution(b) Dissolve 5 mg of Carvedilol Impurity C CRS* in 5.0 mL of the mobile phase and dilute to 100.0 mL with the mobilephase. Dilute 4.0 mL of the solution to 100.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 10.0 mL withthe mobile phase.(c) Dissolve 5 mg of Carvedilol for system suitability CRS* (containing Impurities A and D) in the mobile phase anddilute to 50.0 mL with the mobile phase.ColumnSize150 x 4.6 mmStationary PhaseEnd-capped octylsilyl silica gel for chromatography R (5 µm)Temperature55 CMobile PhaseDissolve 1.77 g of potassium dihydrogen phosphate R in water and dilute to 650 mL with the same solvent; adjust topH 2.0 with phosphoric acid R and add 350 mL of acetonitrile RFlow Rate1.0 mL/minDetectionSpectrophotometer @ 240 nmInjection20 µLRun Time6 times the retention time of CarvedilolRelative Retention with Reference to Carvedilol (about 4 min)**Impurity Aabout 0.5Impurity Cabout 2.9Impurity Dabout 3.8System SuitabilityReference Solution (b)Minimum resolution of 3.5 between peaks due to Impuritiy A and Carvedilol*Carvedilol Impurity C CRS (Y0000103) and Carvedilol for system suitability CRS (Y0001426) were purchased from European Directorate for the Quality of Medicines & HealthCare(EDQM) – Council of Europe; Postal address: 7 Allee Kastner CS 30026F - 67081 STRASBOURG (France).** Retention times, relative retentions, and retardation factors are provided for information only and are not mandatory, no deviation allowance is defined.219331Method 1Original Method as Described in the MonographColumn: Kinetex Core-Shell C8 5 µmDimensions: 150 x 4.6 mmPart No.: 00F-4608-E0Flow Rate: 1.0 mL/minSample: 1. Impurity A2. Carvedilol3. Impurity C4. Impurity DElution Time of Last Peak: 21.53 minRs Impurity A and Carvedilol: 10.23App ID 21933423010Phenomenex5l10WEB: www.phenomenex.com15202530min

(European Pharmacopeia 9.0, Chapter 2.2.46. Chromatographic separation techniques)Method ParameterAllowed Adjustments(isocratic elution)Method 1Mobile Phase pH 0.2 units2.0 (as specified)Concentration of Salts in Buffer 10 %As specified in Monograph 1745 Details TableComposition of the Mobile Phase 30 % of the minor solvent component relative or 2 %absolute, whichever is the larger. No other componentis altered by more than 10 % absolute.As specified in Monograph 1745 Details TableWavelength of DetectorNo deviations permitted240 nm (as specified)Injection VolumeMay be decreased, provided detection and repeatability of the peak(s) to be determined are satisfactory.20 µL (as specified)Column Temperature 10 C55 C (as specified)Stationary PhaseNo change of the identity of the substituent permitted(e.g. no replacement of C8 by C18)Octylsilyl silica gel for chromatography(as specified)Column Length 70 %150 mm (as specified)Column Internal Diameter 25 %4.6 mm (as specified)Particle Size-50 %5 µm (as specified)Flow Rate 50 %1.0 mL/min (as specified)PhenomenexlWEB: www.phenomenex.comEuropean Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsAdjustments for Meeting System Suitability11

European Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsClarithromycinand Related SubstancesPh. Eur. monograph H3OThe Ph. Eur. Monograph 1651 outlines the separation of Clarithromycin from impurities. This method wasstudied and improvements were made to provide faster separations within allowable adjustments.H3COCH3CH3OHClarithromycinPh. Eur. Monograph 1651 DetailsReference Solution(d) Dissolve 15 mg of Clarithromycin for peak identification CRS* in 5 mL of acetonitrile and dilute to 10 mL with waterColumnSize100 x 4.6 mmStationary PhaseOctadecylsilyl silica gel for chromatography R (3.5 µm)Temperature40 CMobile PhaseA: 4.76 g/L solution of potassium dihydrogen phosphate adjusted to pH 4.4 with dilute phosphoric acidB: AcetonitrileGradientTime (min)0 – 32 min32- 34 minFlow Rate1.1 mL/minDetectionSpectrophotometer @ 205 nmInjection10 µL%B25 6060Relative Retention with Reference to Clarithromycin (about 11 min)**Impurity Aabout 0.42Impurity Jabout 0.63Impurity Labout 0.74Impurity Babout 0.79Impurity Mabout 0.81Impurity Cabout 0.89Impurity Dabout 0.96Impurity Nabout 1.15Impurity Eabout 1.27Impurity Fabout 1.33Impurity Pabout 1.35Impurity Oabout 1.41Impurity Kabout 1.59Impurity Gabout 1.59Impurity Habout 1.82System SuitabilityPeak-to-Valley RatioMinimum 3.0, where Hp height above the baseline of the peak due to Impurity D and Hv height above the baseline ofthe lowest point of the curve separating this peak from the peak due to Clarithromycin in the chromatogram obtained withreference solution D* Ph. Eur. Standard Clarithromycin for peak identification CRS Y0000321 was purchased from European Directorate for the Quality of Medicines & HealthCare (EDQM) – Council ofEurope; Postal address: 7 Allée Kastner CS 30026F - 67081 STRASBOURG (France).** Retention times, relative retentions, and retardation factors are provided for information only and are not mandatory, no deviation allowance is defined.12PhenomenexlWEB: www.phenomenex.com

Column: Kinetex Core-Shell XB-C18 3.5 µmDimensions: 100 x 4.6 mmPart No.: 00D-4744-E0Achieve improved sensitivity and resolutionusing Kinetex Core-Shell ColumnsFlow Rate: 1.1 mL/minSample:71. Impurity I2. Impurity A3. Impurity L4. Impurity B5. Impurity C6. Impurity D7. Clarithromycin8. Impurity E9. Impurity F10. Impurity P11. Impurity G12. Impurity HElution Time of Last Peak: 17.1 minPeak-to-Valley Ratio: 10.811865941App ID 235032121030102030minAdjustments for Meeting System Suitability(European Pharmacopeia 9.0, Chapter 2.2.46. Chromatographic separation techniques)Allowed AdjustmentsMethod Parameter(isocratic elution)Method 1Mobile Phase pH 0.2 unitsAs specifiedConcentration of Salts in Buffer 10 %As specified in Monograph 1651 Details TableComposition of the Mobile Phase 30 % of the minor solvent component relative or 2 % absolute,whichever is the larger. No other component is altered by morethan 10 % absolute.As specified in Monograph 1651 Details TableWavelength of DetectorNo deviations permitted205 nm (as specified)Injection VolumeMay be decreased, provided detection and repeatability of thepeak(s) to be determined are satisfactory.1 µL (as specified)Column Temperature 10 C40 C (as specified)Stationary PhaseNo change of the identity of the substituent permitted(e.g. no replacement of C18 by C8)Octadecylsilyl silica gel for chromatography(as specified)Column Length 70 %100 mm (as specified)Column Internal Diameter 25 %4.6 mm (as specified)Particle Size-50 %3.5 µm (as specified)Flow Rate 50 %1.1 mL/min (as specified)PhenomenexlWEB: www.phenomenex.comEuropean Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsMethod 1Original Method as Described in the Monograph13

European Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsFluconazoleand Related SubstancesPh. Eur. monograph 2287The Ph. Eur. Monograph 2287 outlines the separation of Fluconazole from impurities. This method wasstudied and improvements were made to provide faster separations within allowable adjustments.FluconazolePh. Eur. Monograph 2287 DetailsReference Solution(b) Dissolve 5.0 mg of Fluconazole for peak identification CRS* (containing Impurity A) in the mobile phase, sonicate ifnecessary, and dilute to 10 mL with the mobile phase(c) Dissolve 3.0 mg of Fluconazole Impurity B CRS* in the mobile phase, sonicate if necessary, and dilute to 100 mL with themobile phase(d) Dissolve 3.0 mg of Fluconazole Impurity C CRS* in the mobile phase and dilute to 20 mL with the mobile phaseColumnSize150 x 4.6 mmStationary PhaseOctadecylsilyl silica gel for chromatography R1 (5 µm)Temperature40 CMobile PhaseAcetonitrile R, 0.63 g/L solution of ammonium formate R (14:86 V/V)Flow Rate1.0 mL/minDetectionSpectrophotometer @ 260 nmInjection20 µLRun Time3.5 times the retention time of FluconazoleRelative Retention with Reference to Fluconazole (about 11 min)**Impurity Babout 0.4Impurity Aabout 0.5Impurity Cabout 0.8System SuitabilityReference Solution (a)Minimum resolution of 3.0 between peaks due to Impurity C and Fluconazole* Fluconazole for peak identification CRS (Y0000558), Fluconazole Impurity B CRS (Y0000573) and Fluconazole Impurity C CRS (Y0000574) were purchased from European Directoratefor the Quality of Medicines & HealthCare (EDQM) – Council of Europe; Postal address: 7 Allee Kastner CS 30026F - 67081 STRASBOURG (France).** Retention times, relative retentions, and retardation factors are provided for information only and are not mandatory, no deviation allowance is defined.Method 1Original Method as Described in the MonographColumn: Luna C18(2) 5 µm Fully PorousDimensions: 150 x 4.6 mmPart No.: 00F-4252-E0Flow Rate: 1.0 mL/minSample: 1. Impurity B2. Impurity A3. Impurity C4. Fluconazole24103Elution Time of Last Peak: 15.9 minRs Impurity C and Fluconazole: 4.39App ID 24103413214024PhenomenexlWEB: www.phenomenex.com6810121416min

Column: Luna C18(2) 3 µm Fully Porous24104Dimensions: 100 x 4.6 mmPart No.: 00D-4251-E04Flow Rate: 1.5 mL/minSample: 1. Impurity B2. Impurity A3. Impurity C4. FluconazoleElution Time of Last Peak: 7.97 minApp ID 24104Rs Impurity C and Fluconazole: 3.5513202468Adjustments for Meeting System Suitability(European Pharmacopeia 9.0, Chapter 2.2.46. Chromatographic separation techniques)Allowed AdjustmentsMethod Parameter(isocratic elution)Method 1Method 2Mobile Phase pH 0.2 unitsAs specifiedAs specifiedConcentration of Salts in Buffer 10 %As specified in Monograph 2287Details TableAs specifiedComposition of the Mobile Phase 30 % of the minor solvent componentrelative or 2 % absolute, whicheveris the larger. No other component isaltered by more than 10 % absolute.As specified in Monograph 2287Details TableAs specifiedWavelength of DetectorNo deviations permitted260 nm (as specified)As specifiedInjection VolumeMay be decreased, provided detectionand repeatability of the peak(s) to bedetermined are satisfactory.20 µL (as specified)As specifiedColumn Temperature 10 C40 C (as specified)As specifiedStationary PhaseNo change of the identity of the substituent permitted (e.g. no replacementof C18 by C8)Octadecylsilyl silica gel for chromatography (as specified)As specifiedColumn Length 70 %150 mm (as specified)100 mm (-33.3 %)Column Internal Diameter 25 %4.6 mm (as specified)As specifiedParticle Size-50 %5 µm (as specified)3 µm (-40 %)Flow Rate 50 %1.0 mL/min (as specified)1.5 mL/min ( 50 %)PhenomenexlWEB: www.phenomenex.comminEuropean Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsMethod 2Faster Method Within Allowable Adjustments15

European Pharmacopoeia (Ph. Eur.) Monographs for Generic DrugsFluoxetine Hydrochlorideand Related SubstancesPh. Eur. monograph 1104HClThe Ph. Eur. Monograph 1104 outlines the separation of Fluoxetine from impurities. This methodwas studied and improvements were made to provide faster separations within allowable adjustments.Fluoxetine HydrochloridePh. Eur. Monograph 1104 DetailsReference SolutionDissolve 22 mg of Fluoxetine Hydrochloride CRS* in 10.0 mL of a 0.5 M sulfuric acid. Heat at about 85 C for 3 h. Allow tocool. The resulting solution contains considerable quantities of Impurity A and usually also contains 4-trifluoromethylphenol. To 0.4 mL of this solution add 28.0 mg of Fluoxetine hydrochloride CRS*, about 1 mg of Fluoxetine Impurity B CRS*and about 1 mg Fluoxetine Impurity C CRS*, then dilute to 25.0 mL with mobile phase.ColumnSize150 x 4.6 mmStationary PhaseOctylsilyl silica gel for chromatography R (5 µm)Mobile PhaseMix 8 volumes of methanol R, 30 volumes of tetrahydrofuran R, and 62 volumes of a solution of trimethylamine Rprepared as follows: to 10 mL of trimethylamine R, add 980 mL of water R, mix and adjust to pH 6.0 with phosphoric acidR (about 4.5 mL) and dilute to 1000 mL with water R.Flow Rate1.0 mL/minDetectionSpectrophotometer @ 215 nmInjection10 µLRun Time3 times the retention time of FluoxetineRelative Retention with Reference to Fluoxetine (about 10-18 min)**Impurity AImpurity BImpurity Cabout 0.24about 0.27about 0.90System SuitabilityPeak-to-Valley RatioMinimum 11, where Hp height above the baseline of the peak due to Impurity C and Hv height above the baseline ofthe lowest point of the curve separating this peak from the peak due to Fluoxetine.* Fluoxetine hydrochloride CRS (F0253000), Fluoxetine Impurity B CRS (F0253020) and Fluoxetine Impurity C CRS (F0253030) were purchased from European Directorate for theQuality of Medicines & HealthCare (EDQM) – Council of Europe; Postal address: 7 Allee Kastner CS 30026F - 67081 STRASBOURG (France).** Retention times, relative retentions, and retardation factors are provided for information only and are not mandatory, no deviation allowance is defined.241994Method 1Original Method as Described in the MonographColumn: Luna C8(2) 5 µm Fully PorousDimensions: 250 x 4.6 mmPart No.: 00G-4249-E0Flow Rate: 1.0 mL/minSample: 1. Impurity A2. Impurity B3. Impurity C4. FluoxetineElution Time of Last Peak: 10.4 min2Rs Impurity C and Fluoxetine: 2.6631016Phenomenex2lApp ID 24199Peak-to-Valley Ratio: 1146WEB: www.phenomenex.com81012141618min

Method 2Faster Method Within Allowable Adjustments4Column: Kinetex Core-Shell C8 5 µmDimensions: 250 x 4.6 mmPart No.: 00G-4608-E0Flow Rate: 1.0 mL/min2Sample: 1. Impurity A2. Impurity B3. Impurity C4. FluoxetineElution Time of Last Peak: 6.9 minRs Impurity C and Fluoxetine: 2.14App ID 21930Peak-to-Valley Ratio: 1131024681012141618Adjustments for Meeting System Suitability(European Pharmacopeia 9.0, Chapter 2.2.46. Chromatographic separation techniques)Allowed AdjustmentsMethod Parameter(isocratic elution)Method 1Method 2Mobile Phase pH 0.2 units6 (as specified)As specifiedConcentration of Salts in Buffer 10 %As specified

test procedures of the United States Pharmacopeia (USP) and European Pharmacopoeia Monographs (Ph. Eur.). This guide provides analysts with solutions to standard USP and Ph. Eur. Monographs and also incorporates cutting edge Kinetex core-shell LC columns to provide shorter separation times and improved resolution while meeting all the