Simultaneously Determining Seven Second-Line Anti-TB Drugs by UHPLC-MS: Application for TDM in HIV-TB Patients

2021 ◽  
Vol 18 ◽  
Author(s):  
Lin Yin ◽  
Yaru Xing ◽  
Xiaoqin Le ◽  
Jun Chen ◽  
Lin Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Second Line ◽  
Aminosalicylic Acid ◽  
Limit Of Quantification ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
The Future ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean

Background: To optimize therapy for patients with human immunodeficiency virus-tuberculosis (HIV-TB) coinfection, we developed an ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS) method to monitor seven second-line anti-tuberculosis drugs. Methods: Blood samples (n = 70) were collected from 35 patients with HIV-TB coinfection; the plasma sample was protein-precipitated and diluted with a solution containing heptafluorobutyric acid. The plasma concentrations of rifabutin (RBT), clofazimine (CLO), moxifloxacin (MFX), prothionamide (PTH), levofloxacin (LFX), amikacin (AMK), and para-aminosalicylic acid (PAS) were detected by UHPLC-MS/MS method. Results: In these 70 samples, the mean concentrations of RBT, CLO, MFX, PTH, LFX, and AMK were 173.8 (10.0–550.0), 61.1 (54.4–67.7), 646.6 (25.0–2480.0), 120.5 (50.0–597.0), 1565.9 (100.0–3480.0), and 10753.0 (400.0–76 700.0) µg/L, respectively. Only one sample was detected to have PAS with concentration less than the lower limit of quantification. Most of the drug concentrations detected in these patients were lower than the targeted concentrations in TB patients. Conclusion: We created a simple UHPLC-MS method for simultaneously quantifying anti-TB drugs. The plasma concentrations in HIV-TB co-infected patients were lower than the targeted concentrations. It is important to monitor anti-TB drugs in the future. This method will facilitate the monitoring of anti-TB drugs in the future.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Desbutyl-Lumefantrine Is a Metabolite of Lumefantrine with PotentIn VitroAntimalarial Activity That May Influence Artemether-Lumefantrine Treatment Outcome

2011 ◽  
Vol 55 (3) ◽  
pp. 1194-1198 ◽  
Author(s):  
Rina P. M. Wong ◽  
Sam Salman ◽  
Kenneth F. Ilett ◽  
Peter M. Siba ◽  
Ivo Mueller ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Performance ◽  
Geometric Mean ◽  
Artemisinin Combination Therapy ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
The Relationship

ABSTRACTDesbutyl-lumefantrine (DBL) is a metabolite of lumefantrine. Preliminary data fromPlasmodium falciparumfield isolates show greater antimalarial potency than, and synergy with, the parent compound and synergy with artemisinin. In the present study, thein vitroactivity and interactions of DBL were assessed from tritium-labeled hypoxanthine uptake in cultures of the laboratory-adapted strains 3D7 (chloroquine sensitive) and W2mef (chloroquine resistant). The geometric mean 50% inhibitory concentrations (IC50s) for DBL against 3D7 and W2mef were 9.0 nM (95% confidence interval, 5.7 to 14.4 nM) and 9.5 nM (95% confidence interval, 7.5 to 11.9 nM), respectively, and those for lumefantrine were 65.2 nM (95% confidence interval, 42.3 to 100.8 nM) and 55.5 nM (95% confidence interval, 40.6 to 75.7 nM), respectively. An isobolographic analysis of DBL and lumefantrine combinations showed no interaction in either laboratory-adapted strain but mild synergy between DBL and dihydroartemisinin (sums of the fractional inhibitory concentrations of 0.92 [95% confidence interval, 0.87 to 0.98] and 0.94 [95% confidence interval, 0.90 to 0.99] for 3D7 and W2mef, respectively). Using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry assay and 94 day 7 samples from a previously reported intervention trial, the mean plasma DBL was 31.9 nM (range, 1.3 to 123.1 nM). Mean plasma DBL concentrations were lower in children who failed artemether-lumefantrine treatment than in those with an adequate clinical and parasitological response (ACPR) (P= 0.053 versusP> 0.22 for plasma lumefantrine and the plasma lumefantrine-to-DBL ratio, respectively). DBL is more potent than the parent compound and mildly synergistic with dihydroartemisinin. These properties and the relationship between day 7 plasma concentrations and the ACPR suggest that it could be a useful alternative to lumefantrine as a part of artemisinin combination therapy.

scholarly journals High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Buprenorphine Evaluation in Plasma—Application to Pharmacokinetic Studies in Rabbits

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 437
Author(s):  
Marta Tikhomirov ◽  
Błażej Poźniak ◽  
Tomasz Śniegocki
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Studies ◽  
Limit Of Quantification ◽  
Reliable Determination ◽  
Main Challenge ◽  
Analytical Protocol ◽  
Liquid Chromatography Tandem Mass ◽  
Cost Efficient

The precise and reliable determination of buprenorphine concentration is fundamental in certain medical or research applications, particularly in pharmacokinetic studies of this opioid. The main challenge is, however, the development of an analytical method that is sensitive enough, as the detected in vivo concentrations often fall in very low ranges. Thus, in this study we aimed at developing a sensitive, repeatable, cost-efficient, and easy HPLC analytical protocol for buprenorphine in rabbit plasma. In order to obtain this, the HPLC-MS2 system was used to elaborate and validate the method for samples purified with liquid-liquid extraction. Fragment ions 468.6→396.2 and 468.6→414.2 were monitored, and the method resulted in a high repeatability and reproducibility and a limit of quantification of 0.25 µg/L with a recovery of 98.7–109.0%. The method was linear in a range of 0.25–2000 µg/L. The suitability of the analytical procedure was tested in rabbits in a pilot pharmacokinetic study, and it was revealed that the method was suitable for comprehensively describing the pharmacokinetic profile after buprenorphine intravenous administration at a dose of 300 µg/kg. Thus, the method suitability for pharmacokinetic application was confirmed by both the good validation results of the method and successful in vivo tests in rabbits.

Quantification of the Plasma Concentrations of Perampanel Using High-Performance Liquid Chromatography and Effects of the CYP3A4*1G Polymorphism in Japanese Patients

2020 ◽  
Vol 58 (10) ◽  
pp. 915-921
Author(s):  
Sho Ohkubo ◽  
Yumiko Akamine ◽  
Tadashi Ohkubo ◽  
Yuka Kikuchi ◽  
Masatomo Miura
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Clinical Practice ◽  
Plasma Volume ◽  
High Performance ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
Hplc Method ◽  
Limit Of Quantification ◽  
Coefficients Of Variation

Abstract Here, we developed a novel high-performance liquid chromatography (HPLC) method for quantification of perampanel in clinical practice and investigated the relationships between the plasma concentrations of perampanel obtained by this HPLC method and the CYP3A4*1G polymorphism. The developed HPLC method was validated based on US Food and Drug Administration. The developed HPLC method could be performed with a plasma volume of only 200 μL and had a limit of quantification (LOQ) of 2.5 ng/mL. The coefficients of variation (CVs) for intra- and inter-day assays were less than 10.4 and 7.2%, respectively, and the accuracy was &lt;2.4% for both assays. A total of 12 patients who received 2 mg perampanel had C0 values ranging from 70.5 to 451 ng/mL, and the CV showed a large variation of 51.4%. No correlations were observed between the dose-adjusted C0 and the CYP3A4*1G polymorphism. This method was superior to previously reported methods in terms of plasma volume and LOQ and was clinically applicable. Perampanel showed high variations in individual plasma concentrations; however, individual differences could not be predicted from analysis of the CYP3A4*1G polymorphism before perampanel administration. Therefore, after beginning perampanel treatment, the dose should be determined based on the observed plasma concentration.

scholarly journals Aldehydes in Exhaled Breath during E-Cigarette Vaping: Pilot Study Results

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 46 ◽  
Author(s):  
Vera Samburova ◽  
Chiranjivi Bhattarai ◽  
Matthew Strickland ◽  
Lyndsey Darrow ◽  
Jeff Angermann ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
High Performance ◽  
Exhaled Breath ◽  
Cigarette Use ◽  
Methyl Ethyl ◽  
Potential Toxicity ◽  
Limit Of Quantification ◽  
Study Results ◽  
Exposure Levels ◽  
The Mean

Several studies have shown the presence of aldehydes (i.e., formaldehyde, acrolein) in mainstream emissions of some e-cigarettes. For this reason, concerns have been raised regarding potential toxicity. The purpose of this research was to measure levels of carbonyls in exhaled breath of e-cigarette users during “vaping” sessions and estimate the respiratory tract (RT) uptake of specific aldehydes, including formaldehyde and acetaldehyde. We measured concentrations of 12 carbonyls in e-cigarette aerosols produced directly by e-cigarettes and in the exhaled breath of 12 participants (19 sessions). Carbonyls were sampled on 2,4-dinitrophenylhydrazine (DNPH) cartridges and analyzed with high performance liquid chromatography (HPLC) coupled with a UV/Vis photodiode detector. We found that in most cases, levels of aldehydes and methyl ethyl ketone (MEK) were significantly higher (2–125 times) in exhaled e-cigarette breaths than in pre-exposed breath. Exposure levels for the most abundant individual carbonyls in e-cigarette emissions—formaldehyde, acetaldehyde, acrolein—were between the limit of quantification (LOQ) and 24.4 μg·puff−1. The mean retention of formaldehyde in the respiratory tract was 99.7 ± 0.9% for all participants, while acetaldehyde retention was 91.6 ± 9.9%. Within the limitation of a small number of participants, our results showed that there is an increase in breath carbonyls during e-cigarette use.

Increased teniposide clearance with concomitant anticonvulsant therapy.

1992 ◽  
Vol 10 (2) ◽  
pp. 311-315 ◽  
Author(s):  
D K Baker ◽  
M V Relling ◽  
C H Pui ◽  
M L Christensen ◽  
W E Evans ◽  
...  
Keyword(s):  
High Performance ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Substantial Reduction ◽  
Systemic Exposure ◽  
Pharmacokinetic Interaction ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Systemic Clearance ◽  
The Mean

PURPOSE A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. PATIENTS AND METHODS The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. RESULTS The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. CONCLUSION These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.

scholarly journals Simultaneous quantification of cortisol and cortisone in serums and saliva from depressive patients by supported liquid extraction coupled to HPLC–MS/MSs

2020 ◽  
Vol 32 (4) ◽  
pp. 269-275
Author(s):  
Binbin Chen ◽  
Haiyan Lyu ◽  
Xiangzhen Xu ◽  
Chen Wang
Keyword(s):  
High Performance ◽  
Depressive Disorders ◽  
Liquid Extraction ◽  
Butyl Ether ◽  
Limit Of Quantification ◽  
Regulatory Guidance ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Efficient Extraction ◽  
Depressive Patients

Cortisol and cortisone are 2 important glucocorticoids produced in the human hypothalamus–pituitary–adrenal (HPA) axis that respond to stress. An analytical method to determinate cortisol and cortisone in serum and saliva using high-performance liquid chromatography–tandem mass spectrometry following a supported liquid extraction (SLE) was developed. Serum and saliva samples of 0.2 mL were extracted by SLE three times using 0.4 mL of methyl tert-butyl ether each time. The chromatographic separation was obtained on an Agilent Poroshell column using a 0.01% formic acid buffer and acetonitrile (60:40, v/v) as the solvent with a flow rate of 0.3 mL/min. Optimized quantitative mass transitions for cortisol, cortisone, and cortisone d-4 were 363.2/121.0 (m/z), 361.2/163.1 (m/z), and 367.1/270.7 (m/z), respectively. The method validation was achieved according to regulatory guidance. The lower limit of quantification (LLOQ) in serum were 2 ng/mL for cortisol and 1 ng/mL for cortisone, and the LLOQ in saliva were 0.1 ng/mL for cortisol and 0.2 ng/mL for cortisone. The developed method showed convenient and efficient extraction, a lower LLOQ, and a short running time. Modest correlations between serum and saliva cortisol and cortisone concentrations were found. The method was successfully applied in assessing the HPA condition of patients with depressive disorders.

scholarly journals Clozapine and desmethylclozapine: correlation with neutrophils and leucocytes counting in Mexican patients with schizophrenia

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Mayela Vaquero-Baez ◽  
Araceli Díaz-Ruíz ◽  
Luis Tristán-López ◽  
Carlos Aviña-Cervantes ◽  
Carlos Torner ◽  
...  
Keyword(s):  
Plasma Levels ◽  
High Performance ◽  
Adverse Reactions ◽  
Plasma Concentrations ◽  
High Performance Liquid Chromatographic ◽  
Analysis Model ◽  
Ultraviolet Detector ◽  
Drug Concentrations ◽  
Blood Neutrophils ◽  
Schizophrenic Patients

Abstract Purpose The aim of present study is to measure plasma clozapine (CLZ) and N-desmethyl clozapine (DMC) as biomarkers to correlate drug concentrations with the appearance of preclinical adverse hematic effects. Methods A high-performance liquid chromatographic method, using a diode-array (ultraviolet) detector, was validated to obtain reliable concentrations of CLZ and DMC, its main metabolite, in plasma of 41 schizophrenic patients taking CLZ. Blood neutrophils and leucocytes counting were concurrently assessed as a proxy to subclinical adverse reactions. Results The analytical method employed was linear, reproducible, and stable to measure concentrations of CLZ between 30 and 1000 ng/mL, while 12.5–560 ng/mL of the metabolite. The method allowed us to correlate CLZ plasma concentrations, the time taking CLZ and CLZ dose as determinants of neutrophils’ counting with a R2 = 0.447, using a multiple regression analysis model. Likewise, the correlation of leucocyte counting vs CLZ plasma levels and CLZ time, showed a R2 = 0.461. DMC correlated significantly with both neutrophils and leucocytes counting, but was excluded from the regression when CLZ concentration was included in the model. Finally, no other hematological adverse reactions were recorded. One patient presented a cardiovascular complication. The negative correlation between clozapine and neutrophil count observed in patients, suggest that CLZ itself, but not DMC, could be related to hematologic side-effects. Conclusion The findings of this study, demonstrate for the first time, that plasma levels of CLZ and time taking the drug are independent determinants of blood neutrophils and leucocytes, so the monitoring of plasma CLZ may be useful in the clinic practice to determine safe dosing of the drug.

Occurrence and concentrations of residues of tetracyclines, polyether ionophores and anthelmintics in livers of chickens sold in the informal market in Gauteng province, South Africa

2020 ◽  
Author(s):  
Abiodun Adesiyun ◽  
FOLORUNSO O. FASINA ◽  
OVOKEROYE A. ABAFE ◽  
MALESEDI MOKGOATLHENG-MAMOGOBO ◽  
OLUWATOLA ADIGUN ◽  
...  
Keyword(s):  
South Africa ◽  
High Performance ◽  
Maximum Residue Limit ◽  
Regulatory Enforcement ◽  
Gauteng Province ◽  
Informal Market ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Tetracycline Group

The occurrence, concentrations and variables associated with tetracycline, polyether ionophore and anthelmintic residues in the livers of chickens sold in the informal market in South Africa were determined. An ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously analyze for four tetracyclines, five polyether ionophores and six anthelmintic residues. The study determined the presence  of residues  in liver samples at both the limit of quantifications (LoQ) and concentrations over the maximum residue limit (MRLs), i.e. non-compliant. Doxycycline (tetracycline group) was detected in 24.5% (24/98) of chicken livers and 15.3% (15/98) were non-compliant. The mean±SD concentration of 919.04±1081.30 (LoQ) and 1410.57±108.89 ppb (MRL) were obtained. Maduramycin was detected in 27.6% (27/98) of chicken livers and 19.4% (19/98) were non-compliant. The mean±SD for LoQ was 117.96±84.56 and MRL was 153.21±76.29 ppb. The concentrations of residues of doxycycline and maduramycin in chicken livers varied significantly across townships. Lasalocid was quantified in 31.6% (31/98) of the samples, of which 5.1% (5/98) contained concentrations above the MRL. The  mean±SD concentrations of Lasalocid was 62.90±170.84 for samples in which  Lasalocid was quantified and 310.16±356.68 ppb for non-compliant samples. The frequencies of chicken livers that contained detectable concentrations of the three anthelmintic residues were 3.1% (3/98), 1.0% (1/48) and 2.0% (2/98) for praziquantel, closantel and rafoxanide, respectively. The presence of three classes of veterinary drugs residues in chicken liver poses food safety implications to consumers and indicates a need for enhanced regulatory enforcement in controlling these drugs in South Africa.

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