Patent ID: 7038036

Claim:
A method of detecting an antisense oligonucleotide sequence containing stable isotopes, or decomposition products thereof, or an antisense peptide nucleic acid sequence containing stable isotopes, or decomposition products thereof, comprising a step of sampling at least one material to be measured, i.e., blood, tissues, organs, body fluids, cells or excretions from a subject animal to which an antisense oligonucleotide sequence or antisense peptide nucleic acid sequence having a sequence complementary to a desired target sequence to form a hybrid is administered, or a step of sampling subject culture cells to which an antisense oligonucleotide sequence or antisense peptide nucleic acid sequence having a sequence complementary to a desired target sequence to form a hybrid is administered, and a step of measuring the antisense oligonucleotide sequence or decomposition products thereof, or the antisense peptide nucleic acid sequence or decomposition products thereof derived from said sampled material, by nuclear magnetic resonance spectrometry, said antisense oligonucleotide sequence or antisense peptide nucleic acid sequence being the abovementioned antisense oligonucleotide sequence or antisense peptide nucleic acid sequence comprising a single strand RNA or single strand DNA containing at least one nucleotide or peptide nucleic acid as a structural unit, in which at least one structural C atom is substituted by 13 C, and at least one structural N atom is substituted by 15 N, having 10 to 100 bases complementary to the desired target sequence to be hybridized, said oligonucleotide being i) a phosphodiester oligonucleotide wherein 3′-OH and 5′-OH in ribose or deoxyribose are cross-linked by phosphodiester bonds, ii) a phosphorothioate oligonucleotide wherein one or two non cross-linked oxygen atoms in the phosphodiester bonds in said phosphodiester oligonucleotide are substituted by sulfur atoms, or iii) a methylphosphonate oligonucleotide wherein oxygen atoms in the hydroxyl groups in the phosphodiester bonds in said phosphodiester oligonucleotide are substituted by methyl groups, and said peptide nucleic acid having bases, i.e., purine or pyrimidine, and said bases being linked together by peptide bonds to form a 2-aminoethylglycine backbone, wherein more than 90% of the carbon atoms are substituted by 13 C and more than 90% of the nitrogen atoms are substituted by 15 N in every structural unit, i.e., nucleotide or peptide nucleic acid.