Usefulness of virtual parenchymal perfusion software visualizing embolized areas to determine optimal catheter position in superselective conventional transarterial chemoembolization for hepatocellular carcinoma.

AIM: To determine the optimal catheter position during superselective conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) using virtual parenchymal perfusion software. METHODS: Patients who had newly developed HCC nodules ≤6 cm and five or fewer lesions were eligible. The virtual catheter tip was placed on a tumor-feeder identified by TACE guidance software using cone-beam computed tomography during hepatic arteriography to minimize the virtual embolized area (VEA), including the tumor with a safety margin. Conventional transarterial chemoembolization was then carried out at the same position. The VEA and real embolized area where iodized oil was retained on cone-beam computed tomography after cTACE were compared using the dice similarity coefficient, linear regression analysis, and mean surface distance. Technical success of cTACE and therapeutic effects by the modified Response Evaluation Criteria in Solid Tumors were also evaluated. RESULTS: Ninety-one tumors in 56 patients were embolized. The mean dice similarity coefficient values in 80 VEAs and real embolized areas were 0.78 ± 0.01. Both volumes were well correlated (r = 0.957, p < 0.001) with a mean surface distance of 2.78 ± 2.11 mm. Eighty-four (92.3%) tumors were embolized with a safety margin. Regarding the early response of 82 tumors, complete response was achieved in 72 (87.8%), partial response in six (7.3%), and stable disease in four (4.9%). Regarding responses of 81 tumors during the follow-up (mean, 20 ± 4.9 months), complete response was maintained in 62 (76.5%), whereas 19 (23.5%), including six that were incompletely embolized, locally progressed. CONCLUSION: Virtual parenchymal perfusion software can determine the optimal catheter position in superselective cTACE.

Outcomes of Patients with Hepatocellular Carcinoma Treated with Conventional Transarterial Chemoembolization Using Guidance Software.

PURPOSE: To evaluate the outcomes of conventional transarterial chemoembolization using guidance software for hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: One hundred two patients with treatment-naïve HCC with ≤ 7-cm and ≤ 5 lesions treated with conventional transarterial chemoembolization using guidance software were selected. Technical success was classified into 3 grades by computed tomography performed 1 week after transarterial chemoembolization: (i) A, complete embolization with a safety margin; (ii) B, entire tumor embolization without a safety margin; and (iii) C, incomplete embolization. Intrahepatic tumor recurrence was classified into 2 categories: local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Overall survival (OS) and tumor recurrence rates were calculated by the Kaplan-Meier method. Additionally, the incidences of LTP between grade A and B tumors, IDR with/without LTP, and OS with/without LTP were compared by the log-rank test. RESULTS: One hundred fifty-six (82.1%) tumors were determined to be grade A, 26 (13.7%) were determined to be grade B, and 8 (4.2%) were determined to be grade C. The 1-, 3-, and 5-year LTP and IDR rates were 31.7%, 49.4%, and 59.4% and 33.9%, 58.2%, and 73.3%, respectively. LTP developed more frequently in grade B tumors than grade A tumors (P = .0016). IDR developed more frequently in patients with LTP than without LTP (P = .0004). The 1-, 3-, and 5-year OS rates were 96.1%, 71.1%, and 60%, respectively; the 1-, 3-, and 5-year OS rates in patients with/without LTP were 95.7%, 69.8%, and 59.3% and 96.2%, 71.6%, and 59.4%, respectively (P = .9984). CONCLUSIONS: Transarterial chemoembolization guidance software promotes the technical success of transarterial chemoembolization and excellent OS in HCC patients.

Outcomes of conventional transarterial chemoembolization for hepatocellular carcinoma ≥10 cm.

AIM: To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm. METHODS: Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses. RESULTS: Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients. CONCLUSION: Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors.

Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib.

BACKGROUND: This prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice. METHODS: This non-interventional study (NCT02131259) enrolled treatment-naïve and pre-treated patients with inoperable/recurrent EGFR mutation-positive NSCLC, eligible for afatinib treatment as per the afatinib label in Japan. Patients received afatinib at the approved dose (20, 30, 40, or 50 mg/day; physician decision), and were observed following treatment initiation for 52 weeks or until premature discontinuation. Primary endpoint was the incidence of adverse drug reactions (ADRs). Secondary endpoints included ADRs of special interest, and objective response rate (ORR). Post hoc Cox multivariate analyses were used to assess prognostic factors associated with the incidence of ADRs. RESULTS: 1602 patients, at 374 sites (April 2014-March 2015), were included in the analysis; 307 (19%) were aged ≥ 75 years. The most frequently reported ADRs (all/grade 3-4) were diarrhea (78%/15%), rash/acne (59%/6%), stomatitis (31%/4%), and nail effects (38%/4%). Serious ADRs resulting in death occurred in 18 patients (1%). 762 patients (48%) had ≥ 1 afatinib dose reduction and 366 (23%) discontinued due to ADRs; the most common reason for both was diarrhea (8.2% and 6.7%, respectively). ORR was 40.1%. CONCLUSIONS: Real-world treatment of 1602 Japanese patients with afatinib was associated with a predictable ADR profile. Afatinib showed effectiveness in inoperable/recurrent EGFR mutation-positive NSCLC, especially as first-line treatment. As with other EGFR TKIs, prompt management of adverse events is needed in the Japanese population, to reduce serious events and outcomes, including interstitial lung disease.

Correction to: Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib.

The original article can be found online.

Quantitative and antioxidative behavior of Trolox in rats' blood and brain by HPLC-UV and SMFIA-CL methods.

Trolox, a water-soluble vitamin E analogue has been used as a positive control in Trolox equivalent antioxidant capacity and oxygen radical antioxidant capacity assays due to its high antioxidative effect. In this study, the ex vivo antioxidative effects of Trolox and its concentration in blood and brain microdialysates from rat after administration were evaluated by newly established semi-microflow injection analysis, chemiluminescence detection and HPLC-UV. In the administration test, the antioxidative effect of Trolox in blood and brain microdialysates after a single administration of 200 mg/kg of Trolox to rats could be monitored. The antioxidative effects in blood (12.0 ± 2.1) and brain (8.4 ± 2.1, × 10(3) antioxidative effect % × min) also increased. Additionally, the areas under the curve (AUC)s0-360 (n = 3) for blood and brain calculated with quantitative data were 10.5 ± 1.2 and 9.7 ± 2.5 mg/mL × min, respectively. This result indicates that Trolox transferability through the blood-brain barrier is high. The increase in the antioxidative effects caused by Trolox in the blood and brain could be confirmed because good correlations between concentration and antioxidative effects (r ≥ 0.702) were obtained. The fact that Trolox can produce an antioxidative effect in rat brain was clarified.

Validation of an LC-MS/MS Method for the Determination of Propofol, Midazolam, and Carbamazepine in Rat Plasma: Application to Monitor Their Concentrations Following Co-administration.

Propofol (PRO) is a hypnotic used to induce and maintain general anesthesia. A risk of drug-drug interactions exists in cases of clinical co-administration of PRO and midazolam (MDZ) or carbamazepine (CBZ). Therefore a sensitive and rapid assay is needed to monitor these drugs. In this study, a sensitive and selective liquid chromatography-tandem mass spectrometry technique was developed for simultaneous determination of PRO, MDZ, and CBZ in plasma. Simultaneous selected reaction monitoring in the positive and negative ionization modes was used for mass detection. Analytes were isolated from plasma samples by a simple, economic, and rapid solid-phase extraction method. Chromatographic separations were achieved using a Chromolith Performance RP-18e analytical column (100×4.6 mm i.d.) with a mixture of acetonitrile-ammonium acetate buffer (10 mM, pH 3.5) (90 : 10, v/v) as the mobile phase. The method was fully validated for PRO, MDZ, and CBZ over concentrations ranging at 1-100, 2-100, and 7-1000 ng/mL, respectively, with acceptable validation parameters. Furthermore, the method was applied to monitor PRO and MDZ or CBZ following co-administration in rats.

Simultaneous determination of propofol and remifentanil in rat plasma by liquid chromatography-tandem mass spectrometry: application to preclinical pharmacokinetic drug-drug interaction analysis.

Propofol (Pro) is an ultra-short-acting hypnotic agent used for general anesthesia that has no analgesic properties. Remifentanil (Rem) is an ultra-short-acting opioid administered concomitantly as an analgesic with Pro. To evaluate the pharmacokinetic interactions between Pro and Rem, we developed and validated a method combining high-performance liquid chromatography with tandem mass spectrometry for simultaneous determination of Pro and Rem. The proposed method was successfully used to study the pharmacokinetic interactions of Pro and Rem coadministered to rats.

Quantitation of sulfur-containing amino acids, homocysteine, methionine and cysteine in dried blood spot from newborn baby by HPLC-fluorescence detection.

Sulfur-containing amino acids (SAAs), homocysteine (Hcy), methionine (Met) and cysteine (Cys) in blood are related to homocystinuria, an inborn error of metabolism. In this study, an assay method with HPLC-fluorescence detection to quantify the SAAs in a dried blood spot was established and applied to samples from newborn babies (n=200). Sample pretreatment involving reduction, derivatization with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole, and liquid-liquid extraction with ethyl acetate gave the separation of the derivatives with retention times within 12 min. The method was enough sensitive to determine the SAAs in a dried blood spot with 0.04-0.14 µm as the limit of detection at a signal-to-noise ratio of 3. However, the absolute recoveries were very low (5.7% for Hcy, 4.6% for Cys) except for Met (105.4%) owing to inefficient recovery of Hcy and Cys from the blood matrix. Other validation parameters such as accuracy (93.5-106.2%) and intra- (≤ 9.0%) and inter-day precisions (≤ 8.7%) were acceptable. The reliability of a dried blood spot as an analytical sample was estimated. Furthermore, the proposed method was successfully applied to dried blood spots prepared from newborn babies.

Determination of folates by HPLC-chemiluminescence using a ruthenium(II)-cerium(IV) system, and its application to pharmaceutical preparations and supplements.

A chemiluminescence (CL) reaction of folic acid (FA) with ruthenium (II) and cerium (IV) was applied to quantify FA-related compounds such as FA, dihydrofolic acid, tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid and methotrexate (MTX). Among the FAs, 5-methyltetrahydrofolic acid provided the highest CL intensity. HPLC-CL detection of FA was applied to quantify FA in pharmaceutical preparations and supplements. Analytical samples were separated on a semi-micro ODS column with a mixture of 20 mM phosphate buffer (pH 5.7) and acetonitrile (94 : 6, v/v %). The separated samples were mixed with a post-column CL reagent consisting of 1.5 mM Ru(bipy)3 (2+) and 1.0 mM Ce(SO4)2 , then the generated CL was monitored. The calibration range for FA was 10-100 µM and the limit of detection was 1.34 µM (signal-to-noise ratio of 3). Repeatabilities were 4.2, 4.6 and 5.0 RSD% (10, 25, 50 µM), and the recoveries for FA supplement, vitamin B complex supplement and FA-containing medication (tablet) were 102.4 ± 10.5, 103.3 ± 13.3 and 100.3 ± 8.5%, respectively. The described method is robust against changes in the chromatographic parameters of ± 3.3 or ± 1.5%. The measured FA content corresponded well to the labeled content of FA-containing products (100.6-104.9%), demonstrating the precision and accuracy of this method for the evaluation of FA pharmaceutical preparations.

In vitro screening of Fe2+-chelating effect by a Fenton's reaction-luminol chemiluminescence system.

In vitro screening of a Fe(2+) -chelating effect using a Fenton's reaction-luminol chemiluminescence (CL) system is described. The luminescence between the reactive oxygen species generated by the Fenton's reaction and luminol was decreased on capturing Fe(2+) using a chelator. The proposed method can prevent the consumption of expensive seed compounds (drug discovery candidates) owing to the high sensitivity of CL detection. Therefore, the assay could be performed using small volumes of sample solution (150 µL) at micromolar concentrations. After optimization of the screening conditions, the efficacies of conventional chelators such as ethylenediaminetetraacetic acid (EDTA), diethylentriaminepentaacetic acid (DETAPAC), deferoxamine, deferiprone and 1,10-phenanthroline were examined. EC50 values for these compounds (except 1,10-phenanthroline) were in the range 3.20 ± 0.87 to 9.57 ± 0.64 µM (n = 3). Rapid measurement of the Fe(2+)-chelating effect with an assay run time of a few minutes could be achieved using the proposed method. In addition, the specificity of the method was discussed.

Association of microcephalin 1, syntrophin-beta 1, and other genes with automatic thoughts in the Japanese population.

Automatic thoughts may be risk factors for depression and anxiety, and should be detected early. However, the genetic basis of automatic thoughts remains unclear. This study aims to investigate the genetic association of automatic thoughts with SNPs (single nucleotide polymorphisms) involved in cognition, neurogenesis, neuronal cell structure, neurotransmitters, hypothalamus-pituitary adrenal axis and psychiatric illness. The study included 610 healthy participants. We used the Depression and Anxiety Cognition Scale (DACS), a Japanese psychological questionnaire, to assess automatic thoughts. Twenty-five SNPs including COMT, BDNF, FKBP5, SNTB1 (syntrophin-beta 1, rs4512418), and MCPH1 (microcephalin 1, rs2911968) were selected according to their minor allele frequency. Linear regression models were used to test association of mean DACS scores with each allele (major-allele homozygote, heterozygote, and minor-allele homozygote). The significant α-value was set at α < 0.002. Statistical analysis was conducted using SNPStats. Call rates for all genotypes were >98%. Eighteen SNPs did not deviate from Hardy-Weinberg equilibrium, and 7 were excluded from statistical analysis. Significant associations of SNTB1 with interpersonal threat and MCPH1 with future denial were observed only in females. SNTB1 and MCPH1 are located on chromosome 8, which may be involved in neuroticism, avoidant personality and depression. Our results demonstrated that DACS scores showing significant interaction with the 2 SNPs may be regarded as appropriate traits to detect the diathesis of automatic thoughts. The 2 SNPs may be important loci in research on cognitive vulnerability to depression and anxiety.

Simultaneous determination of homocysteine, methionine and cysteine in maternal plasma after delivery by HPLC-fluorescence detection with DBD-F as a label.

An HPLC-fluorescence (FL) method for determination of sulfur-containing amino acids such as homocysteine (Hcy), methionine (Met) and cysteine (Cys) in human plasma was developed. The sulfur-containing amino acids were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F). Calibration curves in the range of 1-100 µm (Hcy and Met) and 5-500 µm (Cys) indicated good linearities (r ≥ 0.998). The limits of detection at a signal-to-noise ratio of 3 were 0.13 (Hcy), 0.02 (Met) and 0.11 µm (Cys), respectively. Acceptable results for accuracy and precision of intra- and inter-day measurements were obtained. The results of Hcy and Cys obtained by the proposed method indicated good correlations with the conventional method (r > 0.911, n = 20). Furthermore, the method was applied to determination of the sulfur-containing amino acids in maternal plasma (n = 200) after delivery. The concentrations of Hcy, Met and Cys as a median (inter quartile range, Q1 and Q3 ) were 5.37 (3.32-7.79) µm, 25.20 (20.10-31.06) µm and 147.25 (102.81-189.31) µm, respectively.

Interaction study of acetylcholinestrase inhibitors on pharmacokinetics of memantine in rat plasma by HPLC-fluorescence method.

The present study aims to investigate the possibility of interaction of donepezil (DP) and galantamine (GAL) as acetylcholinestrase inhibitors, on memantine (MT) hydrochloride in rat plasma by HPLC-fluorescence detection. The separation of MT was achieved within 12 min without interference of DP and GAL on the chromatogram. MT levels in rat plasma with a single administration of MT (2.5 mg/kg, i.p.) and those with a co-administration of DP (5.0 mg/kg, i.p.) and GAL (3 mg/kg, i.p.) were monitored. MT concentrations determined in rat plasma ranged from 10.0 to 245.6 ng/mL. Significant difference was observed in the behavior of MT with a co-administration of DP, while no significant difference was observed with a co-administration of GAL.

Stent Graft Placement for Injured Visceral Artery.

Injury of the visceral artery is a potentially fatal complication of iatrogenic procedures, trauma, and tumors. A stent graft can achieve rapid exclusion of the injured arterial portion and minimize the risk of ischemic complications by preserving arterial flow to organs. Although various types of stent grafts are available worldwide, Viabahn has only been approved for visceral arterial injury in Japan. The reported technical and clinical success rates, including cases with injured pelvic or thoracic arterial branches, are 80%-100% and 66.7%-100%, respectively. Severe ischemic complications are rare; however, fatal ischemia occurs when the stent graft is immediately occluded. The necessity of antiplatelet therapy is controversial, and a target artery diameter ≤ 4 mm is a significantly higher risk factor of stent-graft occlusion.

Escherichia coli O80 in Healthy Cattle: Absence of Shigatoxigenic and Enteropathogenic E. coli O80:H2 and (Phylo) Genomics of Non-Clonal Complex 165 E. coli O80.

The origin of human and calf infections by Shigatoxigenic (STEC) and enteropathogenic (EPEC) Escherichia coli O80:H2 is still unknown. The aim of this study was to identify E. coli O80 in healthy cattle with an emphasis on melibiose non-fermenting E. coli O80:H2. Faecal materials collected from 149 bulls at 1 slaughterhouse and 194 cows on 9 farms were tested with O80 antigen-encoding gene PCR after overnight growth in enrichment broths. The 53 O80 PCR-positive broths were streaked on different (semi-)selective agar plates. Five E. coli colonies from 3 bulls and 11 from 2 cows tested positive with the O80 PCR, but no melibiose non-fermenting E. coli was isolated. However, these 16 E. coli O80 were negative with PCR targeting the fliCH2, eae, stx1, stx2 and hlyF genes and were identified by WGS to serotypes and sequence types O80:H6/ST8619 and O80:H45/ST4175. They were phylogenetically related to E. coli O80:H6 and O80:H45 isolated from different animal species in different countries, respectively, but neither to STEC and EPEC O80:H2/ST301, nor to other serotypes of the clonal complex 165. As a conclusion, healthy adult cattle were not identified as a source of contamination of humans and calves by STEC or EPEC O80:H2.

Virulence of Shigatoxigenic and Enteropathogenic Escherichia coli O80:H2 in Galleria mellonella Larvae: Comparison of the Roles of the pS88 Plasmids and STX2d Phage.

The invasiveness properties of Shigatoxigenic and enteropathogenic Escherichia coli (STEC and EPEC) O80:H2 in humans and calves are encoded by genes located on a pS88-like ColV conjugative plasmid. The main objectives of this study in larvae of the Galleria mellonella moth were therefore to compare the virulence of eight bovine STEC and EPEC O80:H2, of two E. coli pS88 plasmid transconjugant and STX2d phage transductant K12 DH10B, of four E. coli O80:non-H2, and of the laboratory E. coli K12 DH10B strains. Thirty larvae per strain were inoculated in the last proleg with 10 µL of tenfold dilutions of each bacterial culture corresponding to 10 to 106 colony-forming units (CFUs). The larvae were kept at 37 °C and their mortality rate was followed daily for four days. The main results were that: (i) not only the STEC and EPEC O80:H2, but also different E. coli O80:non-H2 were lethal for the larvae at high concentrations (from 104 to 106 CFU) with some variation according to the strain; (ii) the Stx2d toxin and partially the pS88 plasmid were responsible for the lethality caused by the E. coli O80:H2; (iii) the virulence factors of E. coli O80:non-H2 were not identified. The general conclusions are that, although the Galleria mellonella larvae represent a useful first-line model to study the virulence of bacterial pathogens, they are more limited in identifying their actual virulence properties.

Brazilian propolis-derived components inhibit TNF-α-mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes.

BACKGROUND: Previous reports suggest that Brazilian propolis has multiple biological functions and may help to restore adiponectin expression and insulin sensitivity. However, little is known about the molecular mechanisms by which these compounds inhibit the downregulation of adiponectin. METHODS: The effect of various Brazilian propolis-derived components on inhibition of tumor necrosis factor-α (TNF-α)-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes and molecular mechanism was investigated. RESULTS AND CONCLUSIONS: Pretreatment with either artepillin C (C3) or its derivative (C4) significantly inhibited TNF-α-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes. Interestingly, C3 strongly activated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. Treatment of adipocytes with C3 resulted in the upregulation of adiponectin and fatty acid-binding protein 4 expression, but C4 did not significantly induce PPARγ transactivation. C4 did, however, inhibit the TNF-α-induced c-Jun-NH(2)-terminal kinase (JNK) signaling that is involved in adiponectin expression. Molecular docking studies based on hPPARγ with C3 and JNK1 with C4 clearly supported our experimental results. These data demonstrate that 1) both C3 and C4 significantly inhibit the TNF-α-mediated downregulation of adiponectin in adipocytes, 2) C3 functions as a PPARγ agonist, and its inhibition of the effect of TNF-α is due to this PPARγ transactivation, and 3) C4 is an effective inhibitor of JNK activation, thus inhibiting the TNF-α-mediated downregulation of adiponectin. GENERAL SIGNIFICANCE: Brazilian propolis-derived components (C3 and C4) can significantly inhibit TNF-α-mediated downregulation of adiponectin in adipocytes, although they do so via different mechanisms.

Evaluation of hair roots for detection of methamphetamine and 3,4-methylenedioxymethamphetamine abuse by use of an HPLC-chemiluminescence method.

We describe the use of hair roots as a matrix for detection of methamphetamine (MP) and 3,4-methylenedioxymethamphetamine (MDMA) abuse. The concentration of drugs was determined in rat hair roots, hair shafts, and plasma after a single administration of MP or MDMA, by use of an HPLC-peroxyoxalate chemiluminescence (PO-CL) method involving column switching. Plasma and hair roots and shafts were collected from male Wistar rats before and after administration of MP (10 mg kg(-1), i.p.). In addition, the roots and shafts of pigmented and non-pigmented hair of male Lister hooded rats were collected after administration of MDMA (10 mg kg(-1), i.p.). The concentrations of MP and MDMA in plasma and hair were determined by use of the HPLC-PO-CL method, with satisfactory sensitivity and reproducibility. The concentration of MP in hair roots 1-14 days after administration ranged from 0.038 to 0.115 ng mg(-1) (n = 3). By use of the HPLC-PO-CL method, MP could be detected in hair roots for longer (up to 14 days) than it could be detected in conventional biological specimens, for example plasma (~1 day), and MDMA was detected in hair roots from 1 to 10 days after administration. The AUC(1-10) (ng day mg(-1)) for MDMA in roots of non-pigmented and pigmented hair was comparable (4.93 ± 2.09 vs. 6.67 ± 1.28, n = 3), whereas AUC(1-14) for hair shafts differed significantly (1.86 ± 0.93 vs. 4.58 ± 0.63, P < 0.05, n = 3). The window for detecting MP (or MDMA) in hair roots under our conditions was 1-14 (or 1-10) days.

Simultaneous determination of N-benzylpiperazine and 1-(3-trifluoromethylphenyl)piperazine in rat plasma by HPLC-fluorescence detection and its application to monitoring of these drugs.

An HPLC-fluorescence detection method for simultaneous determination of N-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) labeled with 4-(4,5-diphenyl-1 H-imidazol-2-yl)benzoyl chloride (DIB-Cl) was described. DIB-BZP and -TFMPP were well separated within 13 min without interference of peaks from plasma components. The lower detection limits of BZP and TFMPP at a signal-to-noise ratio of 3 were 0.9 and 4.6 ng/mL, respectively. Precisions of the proposed method for intra- and inter-day assays were less than 4.8 and 9.1% as %RSD (n =5). Furthermore, the method could be successfully applied to monitor both compounds in plasma after their sole or co-administration to rats (each dose, 2 mg/kg). Clearance of TFMPP was significantly different under the conditions (P=0.047).