application mass spectrometry in clinical chemistry

Application Mass Spectrometry in Clinical Chemistry

Contents1. Application of MS in Laboratory Medicine

2. Simultaneous Analysis

3. Prospect of Future

Application of MS in Laboratory Medicine

Application of MS in Laboratory Medicine

1. Biochemical genetics 2. Therapeutic Drug monitoring 3. Biomarkers for certain disorders 4. Clinical proteomics 5. Clinical microbiology

Therapeutic Drug monitoring(TDM)

1. Immunoassays(IA)

2. HPLC

3. LC/MS/MS

Immunoassays(IA)

Usage of the instruments for TDM KAQACL in

2011

Cyclosporine

TDM 및 약물남용검사 신빙도조사 결과보고 (2007)

Mass Spectrometry

검사법 비교

Conventional method vs Mass spectrometry

Immunoassays(IA) : Disadvantage

1. 구조가 유사한 compounds (e.g., prodrugs and drug metabolites) 의 교차 -반응에 의한 간섭 1) 간 기능이상 또는 신장기능장애환자에서 더욱 심화 ⇒ 광범위한 수준의 대사물 누적이 발생

2. Human anti-animal antibody 에 의한 간섭효과 1) 치료나 영상촬영을 위한 mouse monoclonal antibody 사용 증가에 따른 human anti-mouse anti body (HAMA)에 의해 잘 인지되지 않음 2) 특히 two-site mouse monoclonal antibody-based 측정법에서 양성과 음성 간섭을 모두 유발

3. 감도 범위가 한정적이다 . 1) 어린아이 간이식 수술 후 tacrolimus 의 경우 IA 로 측정할 때 낮은 감도로 인해 측정이 안 될 수도 있음 .

LC/MS/MS : Advantage

1. Specific (no cross reactivity)

2. Metabolites

3. Cost-effective (?)

Cost-effective

Yearly Costs

　 Total for the IAs LC-MS/MS

Apparatus 20,000 50,000

Maintenance 20,000 20,000

Reagents/consumables 150,000 10,000

Technician(s) 50,000 50,000

Total 240,000 130,000

Ther Drug Monit Volume 31, Number 1, February 2009

Calculations experienced in the authors’ laboratory. Based on 15,000 samples analyzed per year. Prices in Euros including VAT. Ap-paratus costs for the LC-MS/MS are based on 250,000 euro for purchase and 50,000 euro depreciation per year during 5 years.

Conventional method vs Mass spectrometry

1. Automation

2. TAT

3. Method development

Simultaneous Analysis

Unknown Drug Scanning

Antiepileptic Drugs

1. Primidone2. Gabapentin3. Carbamazepine4. Oxcarbazepine5. Zonisamide6. Levetiracetam7. Lamotrigine8. Phenytoin9. Topiramte

MRM chro-matogram

Prospect of Future

• Tests often evolve through this spectrum – New esoteric testing will grow substantially with the maturation of genomics and proteomics – What’s esoteric today may be POCT tomorrow with advances in technology, new therapeutic options, and new care models

Test evolution