Determination of retigabine and its acetyl metabolite in biological matrices by on-line solid-phase extraction (column switching) liquid chromatography with tandem mass spectrometry

Knebel, Norbert; Grieb, Sally; Leisenheimer, S; Locher, Mathias

doi:10.1016/s0378-4347(00)00272-3

Cited by 29 publications

(18 citation statements)

References 16 publications

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“…Even though a relatively significant loss of N-acetyl retigabine was observed during complete removal of its N-glucuronide metabolite by Elution SEP, a two and half times better sensitivity than that published [8] with lower limit of quantitation (LLOQ) of 1.0 ng/mL was still achieved. The LLOQ was determined based on a signal-to-noise (S/N) ratio of at least 10.…”

Section: Specificity Sensitivity and Matrix Effectmentioning

confidence: 73%

“…Even at neutral pH, the fast conversation of N-glucuronide acetyl retigabine to acetyl retigabine was observed using protein precipitation (PPT) without drying and conventional solid phase extraction (data not shown). An on-line LC/MS/MS method [8] provided a fast and sensitive way to determine retigabine and N-acetyl retigabine in biologic matrices. However, during the course of on-line analysis N-glucuronide conjugates of both retigabine and N-acetyl retigabine coexisted with their parent drugs and thus the conversion from the N-glucuronide conjugates to their parent drugs were not avoided.…”

Section: Sample Extraction Optimizationmentioning

confidence: 99%

“…The bioanalytical results of samples with presence of this kind of liable metabolites may lead to false interpretation of pharmacokinetic data and therefore, delay the drug development process [7]. So far, there is only one method being published for the determination of retigabine and N-acetyl retigabine in plasma based on our survey of the literature [8]. Although this on-line LC/MS/MS method was fast and sensitive, the coexisting of N-glucuronide conjugates and their parent drugs in the diluted plasma injection solutions were not avoided and therefore the conversion of N-glucuronide conjugates back to their parent drugs during the course of on-line analysis was not prevented or stopped.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Determination of N-acetyl retigabine in dog plasma by LC/MS/MS following off-line μElution 96-well solid phase extraction

Bu¹,

Nguyen²,

Xu³

et al. 2007

Journal of Chromatography B

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Section: Specificity Sensitivity and Matrix Effectmentioning

confidence: 73%

Section: Sample Extraction Optimizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination of N-acetyl retigabine in dog plasma by LC/MS/MS following off-line μElution 96-well solid phase extraction

Bu¹,

Nguyen²,

Xu³

et al. 2007

Journal of Chromatography B

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“…43 The N-glucuronides of RGB could not be measured in that study because they have been previously shown to be instable in course of bioanalytical procedures and no internal standard is available.…”

Section: Subjects and Study Designmentioning

confidence: 99%

The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine

Hermann¹,

Borlak

Munzel

et al. 2006

Pharmacogenomics J

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Retigabine (RGB) is an investigational antiepileptic drug, which undergoes extensive UGT1A1, 1A9 and 1A4-mediated N-glucuronidation and Nacetylation. The mono-acetylated metabolite of RGB has some pharmacological activity and is denoted AWD21-360. We investigated whether the pharmacokinetics (PK) of RGB and AWD21-360 are altered in subjects with Gilbert's syndrome (GS) and/or with frequent N-acetyltransferase 2 (NAT2) slow acetylator (SA) polymorphisms. Based on consistent genotyping and phenotyping screening results, 37 Caucasian subjects (21-46 years; 31 men, six women) were assigned to one of the following groups:. Subjects received single and multiple (b.i.d.) 200-mg oral RGB doses over 5 days. Blood samples were collected up to 60 h after dosing for plasma PK of RGB and AWD21-360. Group comparisons were performed by ANOVA. Single-dose PK of RGB and AWD21-360 and multipledose PK of RGB did not differ significantly between groups. After multiple dose treatment, RA subjects showed a significantly higher total exposure to AWD21-360 of about 32% (95% CI 101.9-172.5) relative to SA subjects (P ¼ 0.0362). The UGT1A1 metabolic capacity (i.e. presence or absence of GS), however, did not significantly affect the overall exposure to AWD21-360. The results indicate that the PK of RGB is unaltered in individuals with GS, in subjects with NAT2 SA status, and in carriers of both variants, whereas the total exposure to AWD21-360 is significantly related to the RA or SA status of subjects. Results further suggest that metabolic switching to the mono-acetylated metabolite AWD21-360 may partially compensate for the impaired glucuronidation capacity in GS subjects. RGB treatment showed no significant differences in tolerability and safety between groups.

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“…For this reason, the accurate determination of low levels of vitamin D in infant formula is crucial to safeguard the health of infants and children. Traditionally, the existing procedures for vitamin D determination include colorimetric method (Gharbo and Gosser, 1974;Hassan, 1980) Knebel et al, 2000). This study aims to develop vitamin D detection method in infant formula by column-switching high performance liquid chromatography with a rapid automated online extraction procedure without complicated sample cleanup step.…”

Section: Introductionmentioning

confidence: 99%

Development of Vitamin D Determination in Infant Formula by Column-Switching HPLC with UV Detector

Ko¹,

Kwak²,

Ahn³

et al. 2012

Korean Journal for Food Science of Animal Resources

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This study was carried out to develop an analytical method for the determination of vitamin D in infant formula. Vitamin D was determined by column-switching high-performance liquid chromatography (HPLC) equipped with a reversed phase column and UV detector after saponification and extraction of the formula with an organic solvent. A preseparation column (C 8 ), focusing column (C 18 ), analytical column (C 18 ) and UV-Vis detector (254 nm) were used. The limits of detection (LOD) and the limits of quantification (LOQ) for vitamin D were estimated to be 1.51 µg/kg and 4.95 µg/kg, respectively. The linearity, recovery, precision and accuracy of the analytical method for vitamin D were evaluated through the application of a SRM (Standard Reference Material) 1846 (National Institute of Standard & Technology, USA). The linearity of this method was calculated with a value of the coefficient of determination (r 2 ) ≥0.9999. The recovery of vitamin D was 85.20±3.00%. The intra-assay precision for vitamin D was between 1.68±0.03% and 5.75±0.33%, and the inter-assay precision for vitamin D ranged from 1.73±0.03% to 2.96±0.09%. The intra-assay accuracy for vitamin D was between 100.03±2.77% and 102.01±0.59%, and the inter-assay accuracy for vitamin D ranged from 99.00±1.53% to 102.01±3.04%. The proposed method is optimal for the separation and quantification of vitamin D from infant formula.

show abstract

Determination of retigabine and its acetyl metabolite in biological matrices by on-line solid-phase extraction (column switching) liquid chromatography with tandem mass spectrometry

Cited by 29 publications

References 16 publications

Determination of N-acetyl retigabine in dog plasma by LC/MS/MS following off-line μElution 96-well solid phase extraction

Determination of N-acetyl retigabine in dog plasma by LC/MS/MS following off-line μElution 96-well solid phase extraction

The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine

Development of Vitamin D Determination in Infant Formula by Column-Switching HPLC with UV Detector

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