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A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application.

Yang JS, Kim JR, Cho E, Huh W, Ko JW, Lee SY - Ann Lab Med (2015)

Bottom Line: The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99).The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.

View Article: PubMed Central - PubMed

Affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Korea.

ABSTRACT

Background: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode.

Methods: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 µL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-µm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode.

Results: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.

Conclusions: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.

No MeSH data available.


Related in: MedlinePlus

Mean plasma concentrations of (A) sarpogrelate and (B) its metabolite (M-1) after a single oral administration of 100 mg sarpogrelate in 19 healthy male subjects. Bars represent standard errors.
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Figure 2: Mean plasma concentrations of (A) sarpogrelate and (B) its metabolite (M-1) after a single oral administration of 100 mg sarpogrelate in 19 healthy male subjects. Bars represent standard errors.

Mentions: Sarpogrelate demonstrated fast absorption (median tmax approximately 1 hr), and plasma levels of sarpogrelate were below the LLOQ within 6 hr after oral administration. Moreover, sarpogrelate was rapidly converted to M-1, which was measurable for 6 hr. The mean plasma concentration-time profile is shown in Fig. 2. Considerable interindividual variability was observed for the pharmacokinetic parameters of sarpogrelate and M-1, with coefficients of variation >50%. The pharmacokinetic parameters are summarized in Table 3. Under fasting conditions, the mean AUC of sarpogrelate determined here was comparable with those previously reported [9, 10]. The imprecise Cmax and the tmax are most likely due to infrequent sampling.


A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application.

Yang JS, Kim JR, Cho E, Huh W, Ko JW, Lee SY - Ann Lab Med (2015)

Mean plasma concentrations of (A) sarpogrelate and (B) its metabolite (M-1) after a single oral administration of 100 mg sarpogrelate in 19 healthy male subjects. Bars represent standard errors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4446576&req=5

Figure 2: Mean plasma concentrations of (A) sarpogrelate and (B) its metabolite (M-1) after a single oral administration of 100 mg sarpogrelate in 19 healthy male subjects. Bars represent standard errors.
Mentions: Sarpogrelate demonstrated fast absorption (median tmax approximately 1 hr), and plasma levels of sarpogrelate were below the LLOQ within 6 hr after oral administration. Moreover, sarpogrelate was rapidly converted to M-1, which was measurable for 6 hr. The mean plasma concentration-time profile is shown in Fig. 2. Considerable interindividual variability was observed for the pharmacokinetic parameters of sarpogrelate and M-1, with coefficients of variation >50%. The pharmacokinetic parameters are summarized in Table 3. Under fasting conditions, the mean AUC of sarpogrelate determined here was comparable with those previously reported [9, 10]. The imprecise Cmax and the tmax are most likely due to infrequent sampling.

Bottom Line: The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99).The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.

View Article: PubMed Central - PubMed

Affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Korea.

ABSTRACT

Background: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode.

Methods: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 µL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-µm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode.

Results: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.

Conclusions: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.

No MeSH data available.


Related in: MedlinePlus