Determination of S- and R-warfarin enantiomers by using modified HPLC method.

Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical. Method was validated according to ICH guidelines and was found to be sensitive, reliable and less time consuming. For both enantiomers, LLOQ was 12.5 ng/mL. The CV% and accuracy for method were in the range of 0.8-14.6% and 92-107% respectively. The recoveries for both enantiomers were in the range of 86-103.8%. Blood samples were collected from 170 stable patients taking warfarin and S- and R-warfarin levels were determined by this method. Majority of subjects were found to have S/R-warfarin ratio of about 1:2 as reported in previous studies due to rapid clearance of S-enantiomer than R-enantiomer. However individual subjects data was suggestive of presence of slow metabolizers of S-warfarin leading to altered S/R ratio. Previous studies have also pointed out CYP2C9 polymorphism being responsible for such inter-individual differences in S-warfarin metabolism. So plasma warfarin S/R ratio may serve as a useful phenotypic test for CYP2C9 polymorphism.

Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome: A Case Report of a Patient With Multiple Metachronous Malignancies.

Defective repair of DNA when heterozygous leads to Lynch syndrome (LS) which is inherited in an autosomal dominant fashion. When homozygous, defective repair of DNA leads to constitutional mismatch repair deficiency syndrome (CMMRD), inherited in an autosomal recessive fashion with a predisposition to develop a pattern of childhood malignancies including hematological and solid cancers. We report such a case of a 21-year-old male who developed anaplastic astrocytoma, Burkitt lymphoma, osteochondroma, and colon cancer successively. Each cancer was treated successfully except for colon cancer which developed liver metastasis after the initial treatment with curative intent. However, the patient has been treated for liver metastasis with curative intent and is currently on follow-up. This case report highlights the importance of maintaining a low threshold for investigating CMMRD and other potential cancer predisposition syndromes when a patient presents with multiple cancers in the early years of their life.