Enantiospecific drug analysis via the ortho-phthalaldehyde/homochiral thiol derivatization method

Desai, Daksha M.; Gál, J.

doi:10.1016/0021-9673(93)87035-k

Cited by 43 publications

(16 citation statements)

References 35 publications

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“…In the face of a large eudismic ratio, the small amount of stereoisomeric impurity is of minor relevance to the interpretation of the pharmacological data, although < 3 % of eutomer proved to be sufficient to effect markedly higher Y 1 R affinity than expected (K i = 200 nm, Table 1). It should be noted that l-ornithine, the starting material for the synthesis of (S)-6 (Scheme 1), was determined to be enantiomerically pure (investigated by HPLC after derivatisation with ortho-phthalaldehyde and N-acetyl-l-cysteine [22] ). With the intension to extend the experimental applicability of bivalent Y 1 R ligands as pharmacological tools, branched linkers bearing a primary amino group for radio-and fluorescence labelling were introduced (Schemes 5 and 6).…”

Section: Pharmacologymentioning

confidence: 99%

Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Keller¹,

Teng²,

Bernhardt³

et al. 2009

ChemMedChem

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Bivalent ligands are potential tools to investigate the dimerisation of G-protein-coupled receptors. Based on the (R)-argininamide BIBP 3226, a potent and selective neuropeptide Y Y(1) receptor (Y(1)R) antagonist, we prepared a series of bivalent Y(1)R ligands with a wide range of linker lengths (8-36 atoms). Exploiting the high eudismic ratio (>1000) of the parent compound, we synthesised sets of R,R-, R,S- and S,S-configured bivalent ligands to gain insight into the "bridging" of two Y(1)Rs by simultaneous interaction with both binding sites of a putative receptor dimer. Except for the S,S isomers, the bivalent ligands are high-affinity Y(1)R antagonists, as determined by Ca(2+) assays on HEL cells and radioligand competition assays on human Y(1)R-expressing SK-N-MC and MCF-7 cells. Whereas the R,R enantiomers are most potent, no marked differences were observed relative to the corresponding meso forms. The difference between R,R and R,S diastereomers was most pronounced (about sixfold) in the case of the Y(1)R antagonist containing a spacer of 20 atoms in length. Among the R,R enantiomers, linker length and structural diversity had little effect on Y(1)R affinity. Although the bivalent ligands preferentially bind to the Y(1)R, the selectivity toward human Y(2), Y(4), and Y(5) receptors was markedly lower than that of the monovalent argininamides. The results of this study neither support the presence of Y(1)R dimers nor the simultaneous occupation of both binding pockets by the twin compounds. However, as the interaction with Y(1)R dimers cannot be unequivocally ruled out, the preparation of a bivalent radioligand is suggested to determine the ligand-receptor stoichiometry. Aiming at such radiolabelled pharmacological tools, prototype twin compounds were synthesised, containing an N-propionylated amino-functionalised branched linker (K(i)> or =18 nM), a tritiated form of which can be easily prepared.

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Section: Pharmacologymentioning

confidence: 99%

Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Keller¹,

Teng²,

Bernhardt³

et al. 2009

ChemMedChem

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“…However, the HPLC method has not been widely utilized, because they are not commercially available. Although Desai and Gal (1993) indicated the detection of RIM after pre-column derivatization with o-phthalaldehyde 2,3,4,6,-tetra-O-acetyl-1-thio-β-dglucopyranoside or 1-thio-β-d-glucose in borate buffer at pH 9.5, the quantitative assay was not established in the rat plasma sample. Recently, we have shown the simple and quantitative analysis of AMA by HPLC after derivatization with OPA and 1-thio-β-d-glucose using 2-adamantanamine hydrochloride (2-ADA) as an internal standard (IS) in human plasma (Higashi and Fujii, 2004).…”

Section: Introductionmentioning

confidence: 97%

Simultaneous determination of amantadine and rimantadine by HPLC in rat plasma with pre-column derivatization and fluorescence detection for pharmacokinetic studies

Higashi

Uemori

Fujii

2005

Biomed. Chromatogr.

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We investigated simultaneous high-performance liquid chromatographic (HPLC) determination of amantadine hydrochloride (AMA) and rimantadine hydrochloride (RIM) levels in rat plasma after fluorescent derivatization with o-phthalaldehyde and 2-mercaptoethanol. Afterwards, the method was applied to determine their pharmacokinetics. The retention times of AMA and RIM derivatives were 12.6 and 22.2 min and the lower limits of detection were 0.025 and 0.016 microg/mL, respectively. The coefficients of variation for intra- and inter-day assay of AMA and RIM were less than 5.1 and 7.6%, respectively. After i.v. administration of AMA or RIM to rats, the total body clearance and distribution volume at the steady-state of RIM were higher than those of AMA. Bioavailability of AMA and RIM was 34.9 and 37.2%, respectively. When AMA and RIM were p.o. co-administered, the area under the plasma concentration--time curve of RIM was significantly lower than that after RIM alone. On the other hand, pharmacokinetic parameters of AMA did not significantly change. These results indicate that our HPLC assay is simple, rapid, sensitive and reproducible for simultaneously determining AMA and RIM concentrations in rat plasma and is applicable to their pharmacokinetic studies. Also, co-administration of AMA and RIM may result in the lack of pharmacological effects of RIM.

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“…In terms of effective separation and sensitive detection, however, only a few FL labels, ie combination of ortho-phtalaldehyde (OPA) and a suitable chiral thiol (eg N-acetyl-L-cysteine or tert-butyloxycarbonyl-L-cysteine, etc. ; Nimura and Kinoshita, 1986;Desai and Gal, 1993), and 1-(9-fluorenyl)ethyl chloroformate (FLEC) (Einarsson et al, 1987), are successfully applied to real sample analysis. 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl isothiocyanate (GITC) (Kinoshita et al, 1981) is another important chromogenic label.…”

Section: Introductionmentioning

confidence: 99%

R(−)‐4‐(3‐Isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole, a fluorescent chiral tagging reagent: sensitive resolution of chiral amines and amino acids by reversed‐phase liquid chromatography

Toyo’oka

Jin

Tomoi

et al. 2001

Biomedical Chromatography

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The usefulness of R(-)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole [R(-)-DBD-PyNCS], a fluorescent chiral tagging reagent, for the determination of racemic amines and amino acids, was studied. The reagent reacted with beta-blockers selected as representative secondary amines to produce corresponding fluorescent diastereomers (excitation at 460 nm and emission at 550 nm). The yields of the derivatization reaction were dependent on the stereostructure arround the NH group in beta-blockers. The resulting diastereomers were completely separated with single chromatographic run using linear gradient elutions by reversed-phase chromatography. R(-)-DBD-PyNCS was also applied to the determination of DL-amino acid, considered to be one of the primary amines, in human urine and foodstuffs. DL-amino acids tested equally reacted with the reagent, and the thiocarbamoyl derivatives were separated with an ODS column. The epimerization during the derivatization reaction was negligible judging from the resolution of opposite diastereomers on the chromatogram. The occurence of D-amino acids (D-Ala, D-Ser, D-Asp and/or D-Glu) was identified in the samples tested. The structures and the purities were elucidated with on-line HPLC-MS. The chiral reagent possessing an isothiocyanate group (-NCS) in the structure seems to be applicable to continuous sequential analysis of peptides containing D-amino acids. The thiocarbamoyl derivatives obtained from the reaction with DL-amino acids were converted to thiohydantoins via thiazolinones in acidic medium. The thiohydantoins produced from acidic, basic, neutral, hydroxyl and aromatic amino acids were completely separated with isocratic elutions using acidic mobile phase containing 0.1% TFA. The separations were sufficient for the identification of DL-amino acid in peptide sequences. Although the epimerization during the conversion reaction to thiohydantoins was not avoidable, the descrimination of D- and L-configuration was demonstrated with some commercially available peptides such as beta-lipotropin and [D-Ala2]-deltorphin II. The Edman degaradation method using R(-)-DBD-PyNCS was also adopted to autoanlaysis by gas-phase sequencer. The separation and the detection (UV 254 nm) conditions of the derivatives were used without any change from those for the Edman degradation method using PITC as the tagging reagent. The three DL-amino acid residues (Tyr, Ala and Gly) in [L-Ala2]-leucine-enkephalin and [D-Ala2]-leucine-enkephalin were perfectly identidied with the autoanalysis.

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Enantiospecific drug analysis via the ortho-phthalaldehyde/homochiral thiol derivatization method

Cited by 43 publications

References 35 publications

Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Simultaneous determination of amantadine and rimantadine by HPLC in rat plasma with pre-column derivatization and fluorescence detection for pharmacokinetic studies

R(−)‐4‐(3‐Isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole, a fluorescent chiral tagging reagent: sensitive resolution of chiral amines and amino acids by reversed‐phase liquid chromatography

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Enantiospecific drug analysis via the ortho-phthalaldehyde/homochiral thiol derivatization method

Cited by 43 publications

References 35 publications

Bivalent Argininamide‐Type Neuropeptide Y Y1 Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Bivalent Argininamide‐Type Neuropeptide Y Y1 Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Simultaneous determination of amantadine and rimantadine by HPLC in rat plasma with pre-column derivatization and fluorescence detection for pharmacokinetic studies

R(−)‐4‐(3‐Isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole, a fluorescent chiral tagging reagent: sensitive resolution of chiral amines and amino acids by reversed‐phase liquid chromatography

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Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation

Bivalent Argininamide‐Type Neuropeptide Y Y₁ Antagonists Do Not Support the Hypothesis of Receptor Dimerisation