ANALYSIS OF CYTOSTATIC COMPOUNDS IN AQUATIC ENVIRONMENT ubomra Kova - - PowerPoint PPT Presentation

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analysis of cytostatic compounds
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ANALYSIS OF CYTOSTATIC COMPOUNDS IN AQUATIC ENVIRONMENT ubomra Kova - - PowerPoint PPT Presentation

Jun 19, 2023 35 likes •185 views

ANALYSIS OF CYTOSTATIC COMPOUNDS IN AQUATIC ENVIRONMENT ubomra Kova ov 1 under the supervision of Juliane Hollender 2 and Wolfgang Dott 1 1 RWTH Aachen University, Institute of Hygiene and Environmental Health 2 EAWAG, Swiss Federal

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SLIDE 1

ANALYSIS OF CYTOSTATIC COMPOUNDS

IN AQUATIC ENVIRONMENT

Ľubomíra Kovaľová1

under the supervision of

Juliane Hollender2 and Wolfgang Dott1

1 RWTH Aachen University, Institute of Hygiene and Environmental Health 2 EAWAG, Swiss Federal Institute of Aquatic Science and Technology

18 January 2006 AQUAbase Workshop on ANALYTICAL METHODS

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SLIDE 2
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

PHARMACEUTICALS IN THE ENVIRONMENT

  • GENERAL AIM:
  • find out ENVIRONMENTAL CONCENTRATIONS
  • check ECOTOXICOLOGY
  • provide ways of ELIMINATION FROM ENVIRONMENT

(if necessary)

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SLIDE 3
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

CYTOSTATICS

  • COMPOUNDS USED IN CHEMOTHERAPY OF PATIENTS

WITH CANCER

  • DESIGNED TO CAUSE MUTATION AND KILL CELLS
  • PRESCRIPTION RATE:

Denmark 2001

cytostatic kg/year HYDROXYCARBAMID 180 5-FLUOROURACIL 8.4 CYCLOPHASPHAMIDE 6.8 METHOTREXATE 1.0 IFOSFAMIDE 0.9 ETOPOSIDE 0.7

Uniklinik Aachen 2004

cytostatic kg/year 5-FLUOROURACIL 2.9 CYTARABINE 1.0 IFOSFAMIDE 1.0 CYCLOPHOSPHAMIDE 0.8 GEMCITABINE 0.7 MEHOTREXATE 0.6

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SLIDE 4
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

Uniklinik Aachen 2004

cytostatic kg/year 5-FLUOROURACIL 2.9 CYTARABINE 1.0 GEMCITABINE 0.7

HOSPITAL WASTEWATER

µg/l 7.4 2.7 1.8

N N O O N O O O N N O O F N O O F N N O O F

5-FLUOROURACIL CYTARABINE GEMCITABINE unmetabolised ng/l 740 270 180 10%

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SLIDE 5

ACIDIC ACIDIC ACIDIC ACIDIC ACIDIC BASIC BASIC

  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

N N O O F N N O O N O O O N N O O F N O O F

5-FLUOROURACIL CYTARABINE GEMCITABINE Metabolites: 5-fluorouridine 5-fluoro- uracil 1-β-D- 2’,2’-difluoro- 2′-deoxyuridine arabinofuranoside deoxyuridine

N N O O O O O O F

N N O O O O O F

N N O O O O O O N N O O O O O F F

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SLIDE 6
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL CHALLENGE

  • VERY POLAR COMPOUNDS

Log Kow -0.8 to -2.3

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SLIDE 7
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD CLEAN-UP/ PRECONCEN- SEPARATION DETECTION TRATION

SPE HPLC MS/MS

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SLIDE 8
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD HPLC SEPARATION I.

RP columns separation retention

Synergi Hydro

Phenomenex

Aqua

Phenomenex

Polaris C18-Ether

Varian

Synergi Polar

Phenomenex

Nucleosil C18

Machery-Nagel

MZ - PAH

MZ

Symmetry C18

Waters

RP – Reversed Phase

CLEAN-UP DETECTION

mAU 10 20 30 40 50 60

0 2 4 6 min

CytR GemC 5-Fu

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SLIDE 9
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD HPLC SEPARATION II.

HILIC columns separation retention

Zorbax NH2

Agilent

TSK-Gel Amide 80

TOSOH Bioscience

ZIC-HILIC

SeQuant

HILIC – Hydrophilic Interaction Chromatography

CLEAN-UP DETECTION

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SLIDE 10
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD DETECTION 5-Fu CytR GemC

  • MS/MS (electrospray ionisation)
  • UV

CLEAN-UP SEPARATION

LOQ [µg/l]

TSQ Quantum 50 5 10 API 4000 0.1 0.5 0.5 HP 1100 300 500 500

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SLIDE 11
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD CLEAN-UP / PRECONCENTRATION RP mechanism (pH adjusted to keep analytes neutral) acidic basic analytes analytes

ISOLUTE ENV+

IST

Strata-X

Phenomenex

Oasis HLB

Waters

SEPARATION DETECTION

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SLIDE 12
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD CLEAN-UP / PRECONCENTRATION Cation Exchange mechanism (pH adjusted to keep analytes

positively charged)

basic analytes

Bond Elut Certify

Varian

Accubond Evidex

Agilent

Bakerbond Narc-2

JT Baker

Strata-XC

Phenomenex

Empore MPC-SD

3M

SEPARATION DETECTION

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SLIDE 13
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

ANALYTICAL METHOD CLEAN-UP / PRECONCENTRATION Cation Exchange mechanism (pH adjusted to keep analytes

positively charged)

basic analytes

SPEC MP1

Ansys

SPEC MP3

Ansys

Speedisk H2O-philic SC-DVB

JT Baker

SEPARATION DETECTION

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SLIDE 14
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

OUTLOOK

  • to complete analytical method:

choice of SPE materials

  • ptimization of SPE procedure

choice of internal standards SUMMARY

  • good HPLC separation and retention using HILIC
  • satisfactory detection
  • selection of SPE retention mechanism for basic

compounds

ENVIRONMENTAL CONCENTRATIONS

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SLIDE 15
  • CONTEXT
  • COMPOUNDS
  • ANALYTICAL

CHALLENGE

  • ANALYTICAL

METHOD

  • OUTLOOK

thank you for your attention