• Journal of Pharmaceutical Investigation
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• v.37 no.1
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• pp.57-62
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two donepezil tablets, $Aricept^{TM}$ tablet (Dae Woong Pharm. Co., Ltd., Korea, reference drug) and $Donpezil^{TM}$ tablet (Dong Wha Pharm. Ind. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing donepezil hydorchloride 10 mg in a $2{\times}2$ crossover study. There was a three-week washout period between the doses. Plasma concentrations of donepezil were monitored by an LC-MS/MS far over a period of 240 hr after the administration. $AUC_t$, (the area under the plasma concentration-time curve from time zero to 240 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$)were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$, No significant sequence effects were found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ and $C_{max}$ were log 0.95${\sim}$log 1.03 and log 0.94${\sim}$log 1.08, respectively. These values were within the acceptable bioequivalence intervals of log 0.80${\sim}$log 1.25. Taken together, our study demonstrated the bioequivalence of $Aricept^{TM}$ and $Donpezil^{TM}$ with respect to the rate and extent of absorption.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.101-106
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• 1998

A bioequivalence study of the Kerola tablets (Dongkwang Pharmaceutical Co., Korea) to the Tarasyn tablets (Roche Co., Korea), formulations of ketorolac trometamine(KTR), was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 10 mg as KTR in a $2\times2$ crossover study. There was a 1-week washout period between the dose. Plasma concentrations of KTR were monitored by an HPLC method for over a period of 12 hr after each administration. AUC (area under the plasma concentration-time curve) was calculated by the linear trapezoidal method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}\;and\;T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than $20\%$ (i.e., 2.31, 8.19 and $0\%$ for AUC, $C_{max}\;and\;T_{max}$, respectively). Minimum detectable differences $(\%)\;at\;\alpha=0.1\;and\;1-\beta=0.8$ were all less than $20\%$ difference in these parameters between the formulations were all over 0.8. The $90\%$ confidence intervals for these parameters were also within $20\%$. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the 2 formulations of KTR are bioequivalent and, thus, may be prescribed interchangeably.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2425-2430
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• 2013

A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water-5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL ($R^2$ > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

• Archives of Pharmacal Research
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• v.24 no.3
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• pp.207-210
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• 2001

A fully automated high performance liquid chromatography with column-switching was developed for the simultaneous determination of KR60436, a new reversible proton pump inhibitor, and its active metabolite O-Demethyl-KR60436 from rat plasma samples. Plasma sample (50$\mu$l) was directly introduced onto a Capcell Pak MF Ph-1 column ($10{\times}4$ mm I.D.) where primary separation was occurred to remove proteins and concentrate target Substances Using acetonitrile-Potassium Phosphate (PH 7, 0.1 M) (2 : 8, v/v). The drug molecules eluted from MF Ph-1 column were focused in an intermediate column ($10{\times}2$ I.D.) by the valve switching step. The substances enriched in intermediate column were eluted and separated on a Vydac 218MR53 column ($250{\times}3.2$ I.D.) using acetonitrilepotassium phosphate (pH 7, 0.02 M) (47:53, v/v) at a flow rate of 0.5 ml/min when the valve status was switched back to A position. The method showed excellent sensitivity (detection limit of 2 ng/ml) with small volume of samples ($50{\mu}$l), good precision and accuracy, and speed (total analysis time 24 min) without any loss in chromatographic efficiency. The response was linear ($r^2{\geq}0.797$) over the concentration range of 5-500 ng/ml.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.311-317
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• 2004

A bioequivalence study of $Gomcillin^{TM}$ capsules (DAEWOONG Pharmaceutical Co., Korea) to $Famoxin^{TM}$ capsules (Dong Wha Pharm. Ind. Co., Korea) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the amoxicillin dose of 500 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of amoxicillin were monitored by a high-performance liquid chromatography for over a period of 8 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Gomcillin^{TM}/Famoxin^{TM}$ were $log0.91\;{\sim}\;log1.03$ and $;log0.93\;{\sim}\;log1.10$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80\;{\sim}\;log1.25$. Thus, our study demonstrated the bioequivalence of $Gomcillin^{TM}$ and $Famoxin^{TM}$ with respect to the rate and extent of absorption.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Mass Spectrometry Letters
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• v.12 no.1
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• pp.21-25
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• 2021

We aimed to develop and validate a sensitive analytical method of nannozinone A, active metabolite of Nannochelins A extracted from the Myxobacterium Nannocytis pusilla, in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mouse plasma samples containing nannozinone A and 13C-caffeine (internal standard) were extracted using a liquid-liquid extraction (LLE) method with methyl tert-butyl ether. Standard calibration curves were linear in the concentration range of 1 - 1000 ng/mL (r2 > 0.998) with the inter- and intra-day accuracy and precision results less than 15%. LLE method gave results in the high and reproducible extraction recovery in the range of 78.00-81.08% with limited matrix effect in the range of 70.56-96.49%. The pharmacokinetics of nannozinone A after intravenous injection (5 mg/kg) and oral administration (30 mg/kg) of nannozinone A were investigated using the validated LC-MS/MS analysis of nannozinone A. The absolute oral bioavailability of nannozinone A was 8.82%. Plasma concentration of nannozinone A after the intravenous injection sharply decreased for 4 h but plasma concentration of orally administered nannozinone A showed fast distribution and slow elimination for 24 h. In conclusion, we successfully applied this newly developed sensitive LC-MS/MS analytical method of nannozinone A to the pharmacokinetic evaluation of this compound. This method can be useful for further studies on the pharmacokinetic optimization and evaluating the druggability of nannozinone A including its efficacy and toxicity.

• Journal of Nutrition and Health
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• v.44 no.6
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• pp.498-506
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• 2011

This study examined the relationship among plasma homocysteine, folate, and vitamin $B_{12}$ levels and neurocognitive function in 118 community-dwelling elderly subjects (mean age, $75.1{\pm}6.7$ years). The Mini-Mental State Examination (MMSE-KC) was used to screen and assess neurocognitive function in the participants. Dietary intake data including the use of dietary supplements were obtained using the 24-hour recall method by well-trained interviewers. Plasma folate and vitamin $B_{12}$ concentrations were analyzed by radioimmunoassay, and homocysteine was assessed by a high performance liquid chromatography-fluorescence method. The proportions of participants with suboptimal levels of plasma folate (< 3 ng/mL), vitamin $B_{12}$ (< 221 pmol/mL), and homocysteine (> $15{\mu}mol/L$) were 16.1%, 5.9%, and 21.2%, respectively. A multiple regression analysis showed that plasma homocysteine was negatively associated with plasma folate and vitamin $B_{12}$ levels. The MMSE-KC test scores were significantly associated with plasma homocysteine and folate, but not with vitamin $B_{12}$, after adjusting for age, gender, body mass index, living with spouse, education, current smoking, energy intake, and chronic diseases such as hypertension, diabetes, thyroid disease, dyslipidemia, stroke, and cardiovascular disease. A general linear model adjusted for covariates revealed that MMSE-KC test scores increased from the lowest to the highest quartiles of vitamin $B_1$, vitamin $B_2$, vitamin $B_6$, vitamin $B_{12}$, and vitamin C intake (p for trend = 0.012, 0.039, 0.014, 0.046, 0.026, respectively). These results indicate that the problem of folate inadequacy and hyperhomocysteinemia are highly prevalent among community-dwelling elderly people and that dietary intake of the B vitamins and vitamin C is positively associated with cognitive function scores.

• Clinical and Experimental Pediatrics
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• v.59 no.5
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• pp.231-238
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• 2016

Purpose: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. Methods: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. Results: The mean age of the participants was $12.9{\pm}0.3$ years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants ($7.8{\pm}1.9{\mu}g/mL$ vs. $6.0{\pm}1.6{\mu}g/mL$, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. Conclusion: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

• Analytical Science and Technology
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• v.25 no.1
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• pp.19-24
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• 2012

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of ertapenem in human plasma and urine. After addition of internal standard (ceftazidime), plasma and urine was diluted with methanol and analyzed by LC-MS/MS. Using MS/MS with multiple reaction monitoring (MRM) mode, ertapenem were selectively detected without severeinterference from human plasma and urine. The standard calibration curve for ertapenem was linear ($r^2$= 0.9996)over the concentration range 1~100 ${\mu}g/mL$ in human plasma. The intra- and inter-day precision over the concentration range of ertapenem was lower than 8.9% (correlation of variance, CV), and accuracy was between 97.2~106.2%. On the other hand, it was showed good relationship ($r^2$= 0.9992) and the precision (intra- and inter-day) over the concentration range of ertapenem was lower than CV 7.2%, and accuracy was between 97.9~111.6% for urine. This method has been successfully applied to the pharmacokinetic study of ertapenem in human plasma and urine.