Validated UPLC-MS/MS method for the determination of tadalafil in human plasma and its application to a pharmacokinetic study

A simple, rapid, and reliable UPLC-MS/MS method was developed and validated for the determination of tadalafil in human plasma. The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on a Shiseido C18 (100 × 2.1 mm, 2.7 µm) column with isocratic elution using 2.0 mM ammonium acetate and acetonitrile (55:45, v/v) with 0.1% formic acid at a flow rate of 0.7 mL/min. The total run time was 1 min per sample. The quantitative analysis was performed using multiple reaction monitoring at transition of m/z 390.4 → 268.3 for tadalafil and m/z 475.3 → 283.3 for sildenafil as an internal standard. The method was fully validated over a concentration range of 5–1,000 ng/mL with a lower quantification limit of 5 ng/mL. Intra- and inter-day precision (relative standard deviation, %RSD) were within 8.4% and accuracy (relative error, %RE) was lower than -3.2%. The developed and validated method was successfully applied to a pharmacokinetic study of tadalafil (20 mg) in Korean healthy male subjects (n = 12).

Effect of Calcium Source using Tilapia Mossambica Scales on the Bone Metabolic Biomarkers and Bone Mineral Density in Rats

This study was done to evaluate the effect of Ca source using fish (Tilapia mossambica) scales on the bone metabolism. Male Sprague-Dawley rats, 4 weeks of age, were fed low-calcium diet (0.15% Ca) for 2 weeks. The rats on the low-calcium diet were further assigned to one of following three groups for an additional 4 weeks: 1) Ca-depletion group (LoCa) given 0.15% Ca diet (CaCO3), 2) Ca-repletion group (AdCa) given 0.5% Ca diet (CaCO3), 3) Ca-repletion diet (AdFa) received 0.5% Ca diet (Ca source from Tilapia mossambica scales). Serum parathyroid (PTH) and calcitonin showed no differences among experimental groups. Whereas LoCa group elevated the turnover markers, serum ALP and osteocalcin, and urinary deoxypyridinoline (DPD), AdCa and AdFa groups reduced their values. Elevation in the femoral weight, ash and Ca contents was observed in AdCa and AdFa groups. Bone mineral density was increased in AdCa and AdFa groups by 25-26% compared with LoCa group. These data demonstrate that Ca repletion with either Ca source from Tilapia mossambica scales or CaCO3 is similarly effective in the improvement of bone turnover markers and BMD, suggesting the usefulness of Tilapia mossambica scales in the prevention of bone loss compared with CaCO3.

Relationship between Clozapine-Induced Therapeutic Responses and Plasma Homovanillic Acid and 5-Hydroxyindoleacetic Acid Levels in Patients with Chronic Schizophrenia

This study was done to examine changes of plasma homovanillic, acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week clozapine trial and to investigate the relationship between the plasma monoamine metabolites and treatment responses. Twenty-seven chronic schizophrenic patients were treated for 8 weeks with clozapine. The psychopathology was assessed at baseline just clozapine trial and then every 2 weeks until the end of 8-week clozapine treatment using the positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured also biweekly using high preformance liquid chromatography with electrochemical detection method. Plasma HVA and 5-HIAA levels were significantly decreased during a 8-week chozapine treatment, although plasma HVA/5-HIAA ratio showed no significant change. The changes of plasma HVA levels were in significant correlations with the changes of PANSS positive scores, of general psychophathology scores, and changes of total scores. The changes of plasma 5-HIAA levels were in significant correlations with the changes of PANSS negative scores. But the changes of plasma HVA/5-HIAA ratio had no significant correlation with any PANSS subscale score changes. 48% of the patients treated with clozapine was categorized as responders, who showed at least a 20% decrease in PANSS total score and a CGI severity score of mildly ill or less(< or =3) of the end pint of the study. The baseline plasma HVA levels and HVA/5-HiAA) ratio were significantly higher in responders(N=13) than in nonresponders(N=14). But no significant difference in the change of plasma HVA between responders(40.3% decrement) and nonresponders(3.1% increment). But no significant difference in the change of plasma 5-HIAA and the change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. These results suggest that the antipsychotic effect of clozapine on positive symptoms may be associated with dopaminergic blocking activity, and that on negative symptoms may be associated with serotonergic blocking activity. The baseline plasma HVA levels and the change of HVA levels from baseline may be useful predictors of treatment response with clozapine.

Relationship between Risperidone-Induced Therapeutic Response and Plasma Homovanillic Acid and 5-Hydroxyindoleacetic Acid Levels in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVES: This study was purposed to examine the changes of plasma homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week risperidone trial and to investigate the relationship between the plasma monoamine metabolites and risperidone-induced treatment resposes. METHOD: Eighteen schizophrenic patients were treated for 8 weeks with risperidone. The psychopathology was assessed at baseline just before risperidone trial and then at 1st week, 2nd week, 4th week, and 8th week using the Positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured using high performance liquid chromatography with electrochemical detection method. RESULTS: 39% of the patients treated with risperidone was categorized as responders, who showed at least a 20% decrease in PANSS total score at the end point of the study. At the end point of the 1st week, there was significant difference in the percent change of plasma HVA between responders(39% increment) and nonresponders(9% increment). But no significant differences in the percent change of plasma 5-HIAA and the percent change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. CONCLUSION: These results suggest that the magnitude of the early increase of plasma HVA may be associated with risperidone-induced treatment response in schizophrenia.

Comparison of the Treatment Effect Between Higher and Lower Plasma Homovanillic Acid Groups in Schizophrenic Patients / 대한정신약물학회지

This study explored the differences of clinical response, plasma homovanllic acid concentration, haloperidol and reduced haloperidol concentration after 4 weeks haloperidol treatment between higher and lower baseline homovanllic acid concentration groups of schizophrenic patients. After a 2-weeks washout period, they entered the 4 week haloperidol treatment period. The psychopathology was assessed at baseline just before haloperidol trial and then at 1, 2, 4 week using Positive and Negative Syndrome Scale(PANSS). Also the measurement of plasma homovanillic acid(HVA), haloperidol(HP) and reduced haloperidol(RHP) levels were assessed with high performance liquid chromatography at the same time of PANSS assessments. There were no significant differences on the positive, negative, general symptom score of PANSS, haloperidol and reduced haloperidol levels at the end of 4-week between higher plasma HVA group(bsaeline pHVA> or =12.69ng/ml, 10 subjects) and lower plasma HVA group(bsaeline pHVA<12.69ng/ml, 9 subjects). In higher group, the treatment response mainly occured in 2 weeks after treatment, but in lower group, that occured therough 4 weeks. And in higher group, pHVA decresed constantly, but in lower group, pHVA did not changed in 4 weeks. There was significant correlation between plasma haloperidol levels and the clinical improvement(persentile improvement of PANSS positive, general symptom, total score) at the end of 4 week. But no significant correlation were found between plasma reduced haloperidol and RHP/HP ratio and clinical improvement. These results suggest that baseline HVA level is not a valuable therapeutic predictor but it is able to suggest that higher baseline pHVA group and lower group may have different pathophysiology.

Relationship between Therapeutic Response and Plasma HVA/5-HIAA Ratio in Newly Admitted Schizophrenia / 대한정신약물학회지

Twenty newly admitted acute schizophrenic patients were treated with haloperidol for 6 weeks. HVA and 5-HIAA were sampled at baseline, 3days after initial neuroleptic dose, and after 1, 2, 3, 4, 6 weeks of treatment. Nine patients were classified as responders in this prospective haloperidol treatment trial. They had a score of change in the BPRS total scores of 25% or greater. Eleven patients were classified as nonresponders, based on a score of changes in the BPRS total scores of less than 25%. 1) There was no significant difference in plasma HVA/5-HIAA ratio between responder and non-responder before and after haloperidol treatment. 2) There was no significant correlations between plasma HVA/5-HIAA ratio and BPRS total scores. This study could not support the hypothesis that neuroleptic treatment would be effective by changing dopamine and serotonin function and/or by altering their interaction.

A Case of Ael: First report in Korea / 대한수혈학회지

We found a case of Ael for the first time in Korea. The patient was 28-year-old woman admitted for the delivery of her first baby. Patient's red cells were typed as O, while the serum typing was A. The red cells were agglutinated by anti-H, but not agglutinated by anti-A1 or anti-AB. Adsorption of anti-A by patient's RBC was confirmed on the adsorption-elution test. In the saliva, only H substance was demonstable. A substance was not demonstrated either in the serum or in the saliva. A transferase was not demonstrated in patient's serum. One of the patient's sister and her daughter, and the patient's son also had same Ael phenotype.