scholarly journals An Ultrasensitive LC-APPI-MS/MS Method for Simultaneous Determination of Ciclesonide and Active Metabolite Desisobutyryl-Ciclesonide in Human Serum and Its Application to a Clinical Study

2019 ◽  
Vol 5 (1) ◽  
pp. 41-53
Author(s):  
Yu-Luan Chen ◽  
Weimin Wang ◽  
Armand Gatien Ngounou Wetie ◽  
Lei Shi ◽  
John Eddy ◽  
...  
Keyword(s):  
Human Serum ◽  
Active Metabolite ◽  
Reversed Phase ◽  
Serum Samples ◽  
Ionization Source ◽  
Limit Of Quantification ◽  
Incurred Sample Reanalysis ◽  
Phase Liquid ◽  
Novel Method ◽  
Sensitivity Improvement

Abstract Background The development of more efficient drug delivery devices for ciclesonide inhalation products requires an ultrasensitive bioanalytical method to measure systematic exposure of ciclesonide (CIC) and its active metabolite desisobutyryl-ciclesonide (des-CIC) in humans. Method Serum sample was extracted with 1-chlorobutane. A reversed-phase liquid chromatography coupled with atmospheric pressure photoionization–tandem mass spectrometry (LC-APPI-MS/MS) method was used for quantification of 1–500 pg/mL for both analytes in a 0.500-mL serum. The analysis time was 4.7 min/injection. CIC-d11 and des-CIC-d11 were used as the internal standards. Results Calibration curves showed good linearity (r2 > 0.99) for both analytes. This novel method was precise and accurate with interassay precision and accuracy of all within 9.6% CV and ± 4.0% bias for regular QC samples. Extraction recovery was approximately 85% for both analytes. Serum samples are stable for 3 freeze–thaw cycles, 24 h at bench top, and up to 706 days at both −20 °C and −70 °C. This method was successfully used to support a pharmacokinetic (PK) comparison between the inhalation suspensions and an inhalation aerosol of ciclesonide in healthy participants. The method robustness was also supported by the good incurred sample reanalysis reproducibility. Conclusion APPI, a highly selective and sensitive ionization source, made possible for quantifying CIC and des-CIC with a lower limit of quantification (LLOQ) of 1 pg/mL in human serum by LC-MS/MS. A 10-fold sensitivity improvement from the most sensitive reported method (LLOQ, 10 pg/mL) is essential to fully characterize the PK profiles of CIC and des-CIC in support of the clinical development of the ciclesonide-related medications for patients.

Reversed-phase liquid-chromatographic simultaneous analysis for thiopental and pentobarbital in serum.

1983 ◽  
Vol 29 (6) ◽  
pp. 1097-1100 ◽  
Author(s):  
M Kelner ◽  
D N Bailey
Keyword(s):  
Human Serum ◽  
Sodium Hydroxide ◽  
Reversed Phase ◽  
Therapeutic Monitoring ◽  
Butyl Chloride ◽  
Internal Standards ◽  
Standard Curve ◽  
Dilute Sodium Hydroxide ◽  
Phase Liquid ◽  
Liquid Chromatographic

Abstract We describe a reversed-phase liquid-chromatographic assay suitable for therapeutic monitoring of thiopental and pentobarbital simultaneously in human serum. The drugs are extracted from serum at pH 6.6 into n-butyl chloride containing thiamylal and barbital as the respective internal standards. The compounds are back-extracted into dilute sodium hydroxide, an aliquot of which is submitted to chromatography. The lowest measurable concentrations are 1.0 mg/L for thiopental and 2.0 mg/L for pentobarbital. The standard curve is linear from 0 to 100 mg/L for both. Between-run CVs are: at 25 mg/L, 4.1% (thiopental) and 3.2% (pentobarbital); at 50 mg/L, 2.8% (thiopental) and 3.4% (pentobarbital). Data on patients receiving thiopental and pentobarbital illustrate use of the method.

scholarly journals Simultaneous Quantitation of Isoprenoid Pyrophosphates in Plasma and Cancer Cells Using LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3275 ◽  
Author(s):  
Yashpal Chhonker ◽  
Staci Haney ◽  
Veenu Bala ◽  
Sarah Holstein ◽  
Daryl Murry
Keyword(s):  
Ammonium Hydroxide ◽  
Reversed Phase ◽  
Ion Source ◽  
Farnesyl Pyrophosphate ◽  
Ionization Source ◽  
Limit Of Quantification ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Gradient Condition

Isoprenoids (IsoP) are an important class of molecules involved in many different cellular processes including cholesterol synthesis. We have developed a sensitive and specific LC-MS/MS method for the quantitation of three key IsoPs in bio-matrices, geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP). LC-MS/MS analysis was performed using a Nexera UPLC System connected to a LCMS-8060 (Shimadzu Scientific Instruments, Columbia, MD) with a dual ion source. The electrospray ionization source was operated in the negative MRM mode. The chromatographic separation and detection of analytes was achieved on a reversed phase ACCQ-TAG Ultra C18 (1.7 µm, 100 mm × 2.1 mm I.D.) column. The mobile phase consisted of (1) a 10 mM ammonium carbonate with 0.1% ammonium hydroxide in water, and (2) a 0.1% ammonium hydroxide in acetonitrile/methanol (75/25). The flow rate was set to 0.25 mL/min in a gradient condition. The limit of quantification was 0.04 ng/mL for all analytes with a correlation coefficient (r2) of 0.998 or better and a total run time of 12 min. The inter- and intra-day accuracy (85–115%) precision (<15%), and recovery (40–90%) values met the acceptance criteria. The validated method was successfully applied to quantitate basal concentrations of GPP, FPP and GGPP in human plasma and in cultured cancer cell lines. Our LC-MS/MS method may be used for IsoP quantification in different bio-fluids and to further investigate the role of these compounds in various physiological processes.

scholarly journals Validation and Optimization of a Simple RP-HPLC Method for the Determination of Paracetamol in Human Serum and its Application in a Pharmacokinetic Study with Healthy Bangladeshi Male Volunteers

2015 ◽  
Vol 13 (2) ◽  
pp. 125-131
Author(s):  
Anisa Alam Tanam ◽  
Mohammad Firoz Khan ◽  
Ridwan Bin Rashid ◽  
Md Zakir Sultan ◽  
Mohammad A Rashid
Keyword(s):  
Human Serum ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Immediate Release ◽  
Hplc Method ◽  
Serum Samples ◽  
Limit Of Quantification ◽  
Rp Hplc ◽  
Relative Standard

Acetaminophen (paracetamol) is an analgesic and antipyretic agent with minimum anti-inflammatory properties. In the present study a simple, fast, accurate, precise and reproducible RP-HPLC method has been developed and validated for the quantification of paracetamol in human serum samples using theophylline as internal standard. Protein precipitation with perchloric acid was employed in the extraction of paracetamol and theophylline from biological matrix. The chromatographic separation was accomplished on Phenomenex C18 column with a mobile phase comprising of 0.05 mM sodium sulfate buffer (pH 2.2 ± 0.02 adjusted with phosphoric acid) and acetonitrile at a ratio of 93:7 at a flow rate of 1.0 ml/min. The chromatogram was monitored by UV detection at a wavelength of 254 nm. The method was validated over a linear concentration range of 2-100 ?g/ml and limit of quantification (LOQ) was 1.61 ?g/ml with a correlation coefficient (r2) 0.997. The intra-day and inter-day precision expressed as relative standard deviation were found to be 0.49 - 2.68% and 0.36 - 3.44%, respectively. The average recovery of paracetamol from serum ranged from 99.0 - 106.4%. The method was successfully applied to a pharmacokinetic study after oral administration of immediate release paracetamol tablet (1000 mg) in four healthy Bangladeshi volunteers. The mean Cmax was found to be 11.03 ± 3.21 ?g/ml, which occurred at Tmax of 0.88 ± 0.14 hr. The half life, AUC0-8 and AUC0-? values were found to be 3.09 ± 0.71 hr, 31.06 ± 6.57 hr-?g/ml and 37.92 ± 9.51 hr- ?g/ml, respectively. DOI: http://dx.doi.org/10.3329/dujps.v13i2.21889 Dhaka Univ. J. Pharm. Sci. 13(2): 125-131, 2014 (December)

Determination of beta-carotene and its cis isomers in serum

1990 ◽  
Vol 36 (11) ◽  
pp. 1986-1989 ◽  
Author(s):  
W G Rushin ◽  
G L Catignani ◽  
S J Schwartz
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Human Serum ◽  
High Performance ◽  
Beta Carotene ◽  
Reversed Phase ◽  
Serum Samples ◽  
Analytical Recovery ◽  
Cis Isomer

Abstract All-trans-beta-carotene was resolved from its cis isomers in human serum by reversed-phase "high-performance" liquid chromatography. Absorption spectra of the cis peak suggested that 13-cis-beta-carotene was the predominant cis isomer. Analyses and recovery studies of fresh and stored sera eliminated the possibility that isomerization had occurred in samples during handling or storage. The average analytical recovery was 101.9% for standards of the all-trans-, 9-cis-, and 13-cis-beta-carotene compounds in pooled serum samples. We also demonstrated that cis isomers had not formed after the blood was drawn and that cis isomers of beta-carotene are present at significant concentrations in the human circulation.

A reversed phase liquid chromatographic method for the simultaneous determination of several common penicillins in human serum

1991 ◽  
Vol 5 (2) ◽  
pp. 78-82 ◽  
Author(s):  
E. Mendez-Alvarez ◽  
R. Soto-Otero ◽  
G. Sierra-Paredes ◽  
E. Aguilar-Veiga ◽  
J. Galan-Valiente ◽  
...  
Keyword(s):  
Human Serum ◽  
Simultaneous Determination ◽  
Chromatographic Method ◽  
Reversed Phase ◽  
Liquid Chromatographic Method ◽  
Phase Liquid ◽  
Liquid Chromatographic

scholarly journals A Simple RP?HPLC Method for the Determination of Cefdinir in Human Serum: Validation and Application in a Pharmacokinetic Study with Healthy Bangladeshi Male Volunteers

2012 ◽  
Vol 10 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Golam Mortuza Shahed ◽  
Md Ashik Ullah ◽  
Abdullah Al Abdullah Al ◽  
Maizbha Uddin Ahmed ◽  
Mohammad Safiqul Islam ◽  
...  
Keyword(s):  
Human Serum ◽  
Internal Standard ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Dihydrogen Phosphate ◽  
Serum Samples ◽  
Limit Of Quantification ◽  
Rp Hplc ◽  
Male Volunteers ◽  
The Mean

In the present study, a simple RP?HPLC method with UV detection has been validated to determine cefdinir concentrations in human serum samples and applied to determine the pharmacokinetic parameters of cefdinir in healthy Bangladeshi male volunteers. The mobile phase consisting of a mixture of 0.2 M sodium dihydrogen phosphate buffer (pH 3.2 ± 0.05 adjusted with o-phosphoric acid) and methanol at a ratio of 70:30 (v/v), was pumped at a flow rate of 1.0 ml/min through the C18 column at room temperature and the chromatographic separation was monitored at a wavelength of 254 nm with a sensitivity of 0.0001 AUFS. Cefaclor was used as internal standard. The developed method was selective and linear for cefdinir concentrations ranging from 0.05 to 5 ?g/ml for serum samples. The lower limit of quantification was defined as the lowest concentration on the calibration curve (0.05 ?g/ml) for which an acceptable accuracy of 111.60 % and a precision of 7.65 % were obtained, while the minimum detectable quantity of cefdinir was found to be 0.02 ?g/ml. The intra-day and inter-day coefficient of variation (CV) at 0.05 ?g/ml were 7.65% and 9.72%, respectively. The average recovery of cefdinir from serum was 96.43 %. Acceptable results were obtained during stability study. The mean Cmax of cefdinir was found to be 1.42 ± 0.53 ?g/ml attained at a mean Tmax of 3.81 ± 0.96 hr. The mean elimination half-life was 2.03 hours. This method proved to be simple, accurate and precise for pharmacokinetic and bioequivalence studies of cefdinir.   DOI: http://dx.doi.org/10.3329/dujps.v10i2.11790   Dhaka Univ. J. Pharm. Sci. 10(2): 109-116, 2011 (December)

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