Development and Validation of HPLC and HPTLC Methods for Therapeutic Drug Monitoring of Capecitabine in Colorectal Cancer Patients

2019 ◽  
Vol 57 (10) ◽  
pp. 892-900
Author(s):  
Sonali G Thorat ◽  
Rupesh V Chikhale ◽  
Madhukar R Tajne
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Drug Monitoring ◽  
Combination Therapy ◽  
Drug Monitoring ◽  
High Performance ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Chemotherapy Agent ◽  
Assay Methods ◽  
Colorectal Cancer Patients

Abstract Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug–drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.

scholarly journals ANALYSIS OF 4-HYDROXYCYCLOPHOSPHAMIDE IN CANCER PATIENTS PLASMA FOR THERAPEUTIC DRUG MONITORING OF CYCLOPHOSPHAMIDE

2016 ◽  
Vol 8 (9) ◽  
pp. 194 ◽  
Author(s):  
Yahdiana Harahap ◽  
Christian Samuel ◽  
Rizka Andalusia ◽  
Nadia Farhanah Syafhan
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Cancer Patients ◽  
Drug Monitoring ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Mass Detection ◽  
Column Temperature ◽  
Liquid Chromatography Tandem Mass

<p><strong>Objective</strong><strong>:</strong><strong> </strong>To quantify 4-hydroxycyclophosphamide in cancer patients’ plasma for therapeutic drug monitoring of cyclophosphamide.<strong></strong></p><p><strong>Methods</strong><strong>:</strong><strong> </strong>The blood was collected at 0.5 and 1 h after administration of chemotherapy. Prior to analysis, 4-OHCP in plasma was derivatized with semicarbazide HCl, then was extracted using 4 ml ethyl acetate and finally was determined by Ultra High-Performance Liquid Chromatography–tandem mass spectrometry. Chromatographic separation was conducted using waters acquity BEH C18 column (1.7 μm; 50 mm x 2.1 mm). The mobile phase consisted of formic acid 0.1% and methanol (50: 50, v/v), column temperature 30 °C and flow rate of 0.3 ml/min. Mass detection was performed on waters xevo TQD equipped with an electrospray ionization (ESI) source at positive ion mode in the multiple reaction monitoring (MRM). Cyclophosphamide was detected at m/z 260.968&gt;139.978, 4-hydroxycyclophosphamide-semicarbazide at m/z 338.011&gt;224.97, and hexamethylphosphoramide as internal standard at m/z 180.17&gt;92.08.</p><p><strong>Results</strong><strong>:</strong><strong> </strong>The method was linear in the range of 5–1000 ng/ml for cyclophosphamide and also for 4-hydroxycyclophosphamide. The results showed that the level of 4-OHCP in 39 cancer patients was in the range of 5.02 ng/ml to 832.44 ng/ml.<strong></strong></p><p><strong>Conclusion: </strong>4-hydroxycyclophosphamide was detected on 39 patient samples with the lowest level of 5.40ng/ml and the highest level was 832.44 ng/ml. This can be a parameter that the regiment of cyclophosphamide was effective.</p>

scholarly journals Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Cefiderocol

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 242
Author(s):  
Julia Zimmer ◽  
Anka C. Röhr ◽  
Stefan Kluge ◽  
Jonas Faller ◽  
Otto R. Frey ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
High Performance ◽  
Internal Standard ◽  
Gradient Elution ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Serum Samples

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.

scholarly journals Sensitive and Rapid Quantification of Busulfan in Small Plasma Volumes by Liquid Chromatography–Electrospray Mass Spectrometry

2001 ◽  
Vol 47 (8) ◽  
pp. 1437-1442 ◽  
Author(s):  
Thomas E Mürdter ◽  
Janet Coller ◽  
Alexander Claviez ◽  
Frank Schönberger ◽  
Ute Hofmann ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
High Dose ◽  
Selected Ion Monitoring ◽  
Hematopoietic Stem ◽  
Adults And Children ◽  
Liquid Chromatographic

Abstract Background: High-dose busulfan is widely used in conditioning regimens before hematopoietic stem cell transplantation in both adults and children. Large interindividual variability in pharmacokinetics after oral administration has been reported; therefore, therapeutic drug monitoring of busulfan may decrease the incidence of drug-related toxicity (for example, hepatic venoocclusive disease) and may also improve therapeutic efficacy. Methods: Busulfan concentrations were quantified using 200 μL of plasma and liquid–liquid extraction with diethyl ether after the addition of [2H8]busulfan as the internal standard. Separation and detection of busulfan and [2H8]busulfan were achieved with a LUNA C8 column (5 μm; 150 × 2 mm i.d.) at 30 °C, a HP 1100 liquid chromatography system, and a HP 1100 single-quadrupole mass spectrometer. Busulfan and [2H8]busulfan were detected as ammonium adducts in selected-ion monitoring mode at m/z 264.2 and 272.2, respectively. Results: The calibration curve was linear at 5–2000 μg/L busulfan. Intra- and interassay imprecision (CV) and bias were both &lt;11%. The limits of detection and quantification were 2 and 5 μg/L, respectively. Extraction recovery of busulfan was &gt;87%. Analysis of pharmacokinetics in four patients receiving high-dose busulfan indicated that minimum busulfan concentrations before the next dose were 405–603 μg/L, with no interference observed. Conclusions: The new rapid and sensitive liquid chromatographic–mass spectrometric assay is an appropriate method for quantification of busulfan in human plasma, making therapeutic drug monitoring of busulfan faster and easier in clinical practice.

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