| 1. |
- Damoiseaux, David, et al.
(author)
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Presence of Five Chemotherapeutic Drugs in Breast Milk as a Guide for the Safe Use of Chemotherapy During Breastfeeding : Results From a Case Series.
- 2022
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In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 112:2, s. 404-410
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Journal article (peer-reviewed)abstract
- Little is known about infant's safety of chemotherapy during breastfeeding where evidence is limited to a few case reports. This lack of knowledge has led to a general tendency to advise against breastfeeding during cytotoxic therapy despite the overwhelming benefits that breastfeeding offers to both the mothers and their children. In this case series, the presence of five chemotherapies in breast milk was determined. The aim was to obtain insight into the presence of these drugs in breast milk to inform and help clinicians in making informed decisions for women who want to breastfeed. Three patients collected 24-hour samples of breast milk every day for 1, 2, or 3 weeks after chemotherapy, 210 in total. After determination of drug concentrations, the infant daily dose, relative daily infant dose (RID%) and cumulative RID were calculated. Cumulative RIDs in patients varied from 10% to values lower than 1%. Rich data allowed us to design a table which gives predictions on the amount of days that breast milk has to be discarded to reach cumulative RIDs below 5, 1, and 0.1% for each compound. For cyclophosphamide, paclitaxel, and carboplatin, cumulative RIDs below 1 or 0.1% are reached if breast milk is discarded for 1-3 days after administration. This might suggest that breastfeeding in between cycles is an option. However, other pharmacological parameters should also be taken into consideration. For doxorubicin, also the levels of the active metabolite doxorubicinol need quantification. Similarly, breastfeeding during treatment with cisplatin might give substantial exposure and we advise caution.
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| 2. |
- de Jong, Karen, et al.
(author)
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High accumulation of nivolumab in human breast milk : A case report
- 2023
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In: Biomedicine and Pharmacotherapy. - : Elsevier BV. - 0753-3322 .- 1950-6007. ; 166
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Journal article (peer-reviewed)abstract
- Nivolumab is an immunotherapeutic monoclonal antibody (mAb) that is used for the treatment of several types of cancer. The evidence on its use during lactation is lacking. Here, we report on a 39-year-old woman with metastasized melanoma who was treated with 480 mg nivolumab every four weeks during lactation. Breast milk samples were collected over the course of 34 days, including two cycles of nivolumab. The highest measured concentration of nivolumab during the first cycle was 503 ng/mL at day 13. The cumulative relative infant dose (RID) over the first cycle (28 days) was 9.8 %. The highest overall measured nivolumab concentration was 519 ng/mL at day 33, five days after administration of the second nivolumab cycle. Nivolumab seems to accumulate in breast milk over two consecutive cycles, hence the RIDs of consecutive cycles are expected to be higher. To draw further conclusions regarding safety of breastfeeding during nivolumab therapy, more information about the oral bioavailability of nivolumab in newborns, the nivolumab steady-state concentrations in breast milk and its pharmacodynamic effects are needed.
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| 3. |
- Dorlo, Thomas P C, et al.
(author)
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Development and validation of a quantitative assay for the measurement of miltefosine in human plasma by liquid chromatography-tandem mass spectrometry.
- 2008
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In: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 865:1-2, s. 55-62
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Journal article (peer-reviewed)abstract
- A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of miltefosine is presented. A 250 microL human EDTA plasma aliquot was spiked with miltefosine and extracted by a solid-phase extraction method. Separation was performed on a Gemini C18 column (150 mm x 2.0 mm I.D., 5 microm) using an alkaline eluent. Detection was performed by positive ion electrospray ionization followed by triple-quadrupole mass spectrometry. The assay has been validated for miltefosine from 4 to 2000 ng/mL using 250 microL human EDTA plasma samples. Results from the validation demonstrate that miltefosine can be accurately and precisely quantified in human plasma. At the lowest level, the intra-assay precision was lower than 10.7%, the inter-assay precision was 10.6% and accuracies were between 95.1 and 109%. This assay is successfully used in a clinical pharmacokinetic study with miltefosine.
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| 4. |
- Molenaar-Kuijsten, Laura, et al.
(author)
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Everolimus Concentration in Saliva to Predict Stomatitis : A Feasibility Study in Patients with Cancer.
- 2022
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In: Therapeutic Drug Monitoring. - : Ovid Technologies (Wolters Kluwer Health). - 0163-4356 .- 1536-3694. ; 44:4, s. 520-526
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most patients with cancer treated with everolimus experience stomatitis, which seriously affects the quality of life. The salivary concentrations of everolimus may predict the incidence and severity of stomatitis. The authors aimed to examine whether it was feasible to quantify the everolimus concentration in saliva and subsequently use it to predict stomatitis.METHODS: Saliva and whole blood samples were taken from patients with cancer, who were treated with everolimus in the dosage of either 10 mg once a day or 5 mg twice a day. Everolimus concentrations in saliva samples were measured by liquid chromatography-tandem mass spectrometry. A published population pharmacokinetic model was extended with the everolimus concentration in saliva to assess any association between everolimus in the blood and saliva. Subsequently, the association between the occurrence of stomatitis and the everolimus concentration in saliva was studied.RESULTS: Eleven patients were included in this study; saliva samples were available from 10 patients, including 3 patients with low-grade stomatitis. Everolimus concentrations were more than 100-fold lower in saliva than in whole blood (accumulation ratio 0.00801 and relative standard error 32.5%). Interindividual variability (67.7%) and residual unexplained variability (84.0%) were high. The salivary concentration of everolimus tended to be higher in patients with stomatitis, 1 hour postdose ( P = 0.14).CONCLUSIONS: Quantification of the everolimus concentration in saliva was feasible and revealed a nonsignificant correlation between everolimus concentration in the saliva and the occurrence of stomatitis. If future research proves this relationship to be significant, the everolimus concentration in the saliva may be used as an early predictor of stomatitis without invasive sampling. Thereby, in patients with high salivary everolimus concentrations, precautions can be taken to decrease the incidence and severity of stomatitis.
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| 5. |
- Roseboom, Ignace C, et al.
(author)
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Bioanalytical methods for pharmacokinetic studies of antileishmanial drugs
- 2023
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In: BMC Biomedical chromotography. - : John Wiley & Sons. - 0269-3879 .- 1099-0801. ; 37:7
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Journal article (peer-reviewed)abstract
- Bioanalytical method development and validation for the quantification of antileishmanial drugs are pivotal to support clinical trials and provide the data necessary to conduct pharmacokinetic (PK) analysis. This review provides a comprehensive overview of published validated bioanalytical assays for the quantification of antileishmanial drugs amphotericin B, miltefosine, paromomycin, pentamidine, and pentavalent antimonials in human matrices. The applicability of the assays for leishmaniasis clinical trials as well as their relevance to PK studies with emphasis on the choice of matrix, calibration range, sample volume, sample preparation, choice of internal standards, separation, and detection was discussed for each antileishmanial drug. Given that no published bioanalytical methods included multiple antileishmanial drugs in a single assay although antileishmanial shortened combination regimens currently were under investigation, it was recommended to combine various drugs in a single bioanalytical method. Furthermore, bioanalytical method development regarding target site matrix as well as applying microsampling strategies was recommended to optimize future clinical PK studies in leishmaniasis.
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| 6. |
- Roseboom, Ignace C, et al.
(author)
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Development and validation of a high-performance liquid chromatography tandem mass spectrometry method for the quantification of the antiparasitic and antifungal drug amphotericin B in human skin tissue.
- 2022
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In: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 1206
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Journal article (peer-reviewed)abstract
- Amphotericin B is an antifungal and antiparasitic drug used in first-line treatment of the parasitic neglected tropical disease leishmaniasis. Liposomal amphotericin B is currently studied for the treatment of cutaneous and post-kala-azar dermal leishmaniasis, where the dermis of the skin is infected with Leishmania parasites. For the optimization of known treatment regimens, accurate target-site concentrations of the drug are required. To date, no assay was available to assess human skin concentrations of amphotericin B. We here present a bioanalytical assay for the quantification of amphotericin B in 4-mm human skin biopsies. Human skin biopsies were homogenized by overnight digestion using collagenase A and were processed afterwards by simple protein precipitation using methanol. Separation and detection were achieved using a Gemini C18 column with slightly acidic chromatographic conditions and a quadrupole - linear ion trap mass spectrometer, respectively. The method was validated in digestion solution over a range of 10-2,000 ng/mL using natamycin as internal standard, with a correlation coefficient (r2) of at least 0.9974. The assay performance, accuracy and precision, were acceptable over the validated range, using international (EMA and FDA) acceptance criteria. In the skin tissue extracts, amphotericin B ion enhancement was observed, however, the internal standard (IS) corrected for this effect hence calibration standards in digestion solvent could be used as a surrogate matrix for the quantification in skin tissue. Sample preparation recoveries were low (around 27%) because of degradation of amphotericin B during digestion and sample preparation processes, albeit highly reproducible, without compromising the accuracy and precision of the method. Using this assay, amphotericin B could be detected and quantified in skin biopsies originating from treated Indian post-kala-azar dermal leishmaniasis patients.
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| 7. |
- Roseboom, Ignace C, et al.
(author)
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Development and validation of an HPLC-MS/MS method for the quantification of the anti-leishmanial drug miltefosine in human skin tissue.
- 2022
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 207, s. 114402-
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Journal article (peer-reviewed)abstract
- Miltefosine is the only oral drug approved for the treatment of various clinical presentations of the neglected parasitic disease leishmaniasis. In cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis, Leishmania parasites reside and multiply in the dermis of the skin. As miltefosine is orally administered and this drug is currently studied for the treatment of these skin-related types of leishmaniasis, there is an urgent need for an accurate assay to determine actual miltefosine levels in human skin tissue to further optimize treatment regimens through target-site pharmacokinetic studies. We describe here the development and validation of a sensitive method to quantify miltefosine in 4-mm human skin biopsies utilizing high-performance liquid chromatography coupled to tandem mass spectrometry. After the skin tissues were homogenized overnight by enzymatic digestion using collagenase A, the skin homogenates were further processed by protein precipitation and phenyl-bonded solid phase extraction. Final extracts were injected onto a Gemini C18 column using alkaline eluent for separation and elution. Detection was performed by positive ion electrospray ionization followed by a quadrupole - linear ion trap mass spectrometer, using deuterated miltefosine as an internal standard. The method was validated over a linear calibration range of 4-1000 ng/mL (r2 ≥ 0.9996) using miltefosine spiked digestion solution for calibration and quality control samples. Validation parameters were all within internationally accepted criteria, including intra- and inter-assay accuracies and precisions within± 15% and ≤ 15% (within± 20% and ≤ 20% at the lower limit of quantitation). There was no significant matrix effect of the human skin tissue matrix and the recovery for miltefosine, and internal standard were comparable. Miltefosine in human skin tissue homogenates was stable during the homogenization incubation (37 °C,± 16 h) and after a minimum of 10 days of storage at - 20 °C after the homogenization process. With our assay we could successfully detect miltefosine in skin biopsies from patients with post-kala azar dermal leishmaniasis who were treated with this drug in Bangladesh.
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| 8. |
- Roseboom, Ignace C, et al.
(author)
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Development and validation of an ultra-high performance liquid chromatography coupled to tandem mass spectrometry method for the quantification of the antileishmanial drug paromomycin in human skin tissue.
- 2022
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In: Journal of chromatography. B. - : Elsevier. - 1570-0232 .- 1873-376X. ; 1211
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Journal article (peer-reviewed)abstract
- Bioanalytical assay development and validation procedures were performed to quantify antiprotozoal drug paromomycin in human skin tissue by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. Paromomycin, an aminoglycoside drug, is administered intra-muscularly and used in the treatment of multiple clinical presentations of the neglected tropical disease leishmaniasis. It is currently studied in the treatment of post-kala-azar dermal leishmaniasis, a disease where the Leishmania parasites divide and reside in the skin. We present a target-site bioanalytical method to accurately quantify paromomycin in human skin tissue, with the clinical purpose of quantifying paromomycin in skin biopsies from post-kala-azar dermal leishmaniasis patients originating from Sudan. Enzymatic digestion using collagenase A incubated at 37 °C overnight was employed as homogenization method to produce skin tissue homogenates. Further sample preparation was performed by protein precipitation using trichloroacetic acid and a dilution step. Final extracts were injected onto a C18 analytical column and isocratic heptafluorobutyric acid ion-pair separation and elution were employed. The chromatography system was coupled to a triple quadrupole mass spectrometer for detection. The method was validated in digestion solution over a linear range from 5 to 1000 ng/mL (r2 ≥ 0.9967) with the assay performance of accuracy and precision within acceptable criteria values as stated by the EMA guidelines. Furthermore, matrix effects were observed in human skin tissue and were corrected by the multiple deuterated paromomycin internal standard. No substantial IS-normalized matrix effect was detected along with relatively high sample preparation recovery. Consequently, digestion solution matrix serving as the preparation of calibration standards can be used as surrogate matrix for human skin tissue, which is convenient given the limited availability of control matrix. Finally, paromomycin was accurately quantified in skin of post-kala-azar dermal leishmaniasis patients originating from clinical trials in Sudan.
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| 9. |
- Roseboom, Ignace C, et al.
(author)
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Highly sensitive UPLC-MS/MS method for the quantification of paromomycin in human plasma.
- 2020
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 185, s. 113245-
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Journal article (peer-reviewed)abstract
- A highly sensitive method was developed to quantitate the antileishmanial agent paromomycin in human plasma, with a lower limit of quantification of 5 ng/mL. Separation was achieved using an isocratic ion-pair ultra-high performance liquid chromatographic (UPLC) method with a minimal concentration of heptafluorobutyric acid, which was coupled through an electrospray ionization interface to a triple quadrupole - linear ion trap mass spectrometer for detection. The method was validated over a linear calibration range of 5 to 1000 ng/mL (r2≥0.997) with inter-assay accuracies and precisions within the internationally accepted criteria. Volumes of 50 μL of human K2EDTA plasma were processed by using a simple protein precipitation method with 40 μL 20 % trichloroacetic acid. A good performance was shown in terms of recovery (100 %), matrix effect (C.V. ≤ 12.0 %) and carry-over (≤17.5 % of the lower limit of quantitation). Paromomycin spiked to human plasma samples was stable for at least 24 h at room temperature, 6 h at 35 °C, and 104 days at -20 °C. Paromomycin adsorbs to glass containers at low concentrations, and therefore acidic conditions were used throughout the assay, in combination with polypropylene tubes and autosampler vials. The assay was successfully applied in a pharmacokinetic study in visceral leishmaniasis patients from Eastern Africa.
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| 10. |
- Roseboom, Ignace C, et al.
(author)
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Skin tissue sample collection, sample homogenization, and analyte extraction strategies for liquid chromatographic mass spectrometry quantification of pharmaceutical compounds.
- 2020
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 191, s. 113590-
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Journal article (peer-reviewed)abstract
- Quantification of pharmaceutical compounds in skin tissue is challenging because of low expected concentrations, small typical sample volumes, and the hard nature of the skin structure itself. This review provides a comprehensive overview of sample collection, sample homogenization and analyte extraction methods that have been used to quantify pharmaceutical compounds in skin tissue, obtained from animals and humans, using liquid chromatography-mass spectrometry. For each step in the process of sample collection to sample extraction, methods are compared to discuss challenges and provide practical guidance. Furthermore, liquid chromatographic-mass spectrometry considerations regarding the quality and complexity of skin tissue sample measurements are discussed, with emphasis on analyte recovery and matrix effects. Given that the true recovery of analytes from skin tissue is difficult to assess, the extent of homogenization plays a crucial role in the accuracy of quantification. Chemical or enzymatic solubilization of skin tissue samples would therefore be preferable as homogenization method.
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