| 1. |
- Eloff, Emma, et al.
(författare)
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Autoantibodies are major predictors of arthritis development in patients with anti-citrullinated protein antibodies and musculoskeletal pain
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis Group. - 0300-9742 .- 1502-7732. ; 50:3, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Predictors of arthritis development are highly warranted among patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms to optimize clinical management. We aimed to identify clinical and laboratory predictors of arthritis development, including biochemically assessed alcohol consumption, among ACPA-positive patients with musculoskeletal pain.Method: 82 ACPA-positive individuals with musculoskeletal pain but no clinical arthritis were followed for a median of 72 months (interquartile range 57–81 months). We evaluated the prognostic value of baseline clinical and laboratory factors including smoking, symptom duration, age, gender, shared epitope, rheumatoid factor (RF), anti-carbamylated protein antibodies, ACPA levels, erythrocyte sedimentation rate, C-reactive protein levels, tender joint count, patient-reported general well-being, 28-joint Disease Activity Score, and alcohol consumption as measured by phosphatidyl ethanol (PEth) levels in whole blood.Results: During follow-up, 48% developed at least one arthritis. Multivariable analysis revealed an increased risk of arthritis development with RF positivity [hazard ratio (HR) = 2.3, 95% confidence interval (CI) 1.1–4.8, p = 0.028] and higher ACPA levels (HR = 1.0, 95% CI 1.000–1.001, p = 0.002). High levels of RF (HR = 4.4, 95% CI 1.7–11) entailed the highest HR in this ACPA-positive population. Neither clinical characteristics nor alcohol consumption measured by PEth conferred significant prognostic value.Conclusions: ACPA levels and concurrent presence of RF are independent predictors of arthritis development among ACPA-positive patients with musculoskeletal pain. The results are compatible with a dose–response relationship between RA-related autoantibodies and risk of arthritis development.
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| 2. |
- Ginstman, Charlotte, 1975-, et al.
(författare)
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Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls
- 2020
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 30:6, s. 2217-2224
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives.Methods: This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linkoping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18-40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC(0-24h)) was the main outcome measure.Results: There were no significant differences in the studied pharmacokinetic parameters, AUC(0-24h), total AUC, peak serum concentration (C-max), time to peak serum concentrations (T-max), apparent oral clearances of levonorgestrel (CLoral), or terminal half-lives (t1/2) between the groups.Conclusion: This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached.
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| 3. |
- Lood, Yvonne, et al.
(författare)
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Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry : An accurate and sensitive method applied on clinical and forensic samples
- 2021
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 195
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Tidskriftsartikel (refereegranskat)abstract
- A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC-MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4-1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99-101 % and 93-95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.
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| 4. |
- Woksepp, Hanna, et al.
(författare)
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Simultaneous Measurement of 11 Antibiotics for use in the Intensive Care Unit by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry
- 2022
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Ingår i: Therapeutic Drug Monitoring. - Philadelphia, PA, United States : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 44:2, s. 308-318
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies indicate that a high proportion of patients in the intensive care unit (ICU) fail to attain adequate antibiotic levels. Thus, there is a need to monitor the antibiotic concentration to ensure effective treatment. Herein, the authors aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of antimicrobials to assess individualized therapeutic drug monitoring (TDM).METHODS: A UHPLC-MS/MS method with 11 antibiotics (ciprofloxacin, moxifloxacin, benzylpenicillin, levofloxacin, linezolid, rifampicin, meropenem, cloxacillin, cefotaxime, clindamycin, and piperacillin) was developed. Chromatographic separation was performed using a Kinetex biphenyl reversed-phase column, with gradient elution using 0.1% formic acid (FA) and methanol with 0.1% FA. Sample preparation was performed using methanol protein precipitation. The total run time was 5 min.RESULTS: For all analytes, the inter-assay inaccuracies for calibrators were ≤5%. The inter-day inaccuracies for the quality controls (QCs) were ≤5% for all analytes. The inter-assay precision for calibration standards ranged between 1.42% and 6.11%. The inter-assay imprecision for QCs of all antibiotics and concentrations ranged between 3.60% and 16.1%. Inter-assay inaccuracy and imprecision for the QCs and calibration standards were ≤15% for all drugs, except benzylpenicillin.CONCLUSION: A rapid UHPLC-MS/MS method was developed for the simultaneous quantification of 11 different antibiotics. Minimal sample preparation was required to ensure a rapid turnaround time. The method was applied to clinical samples collected from four ICUs.
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| 5. |
- Ärlemalm, Andreas, et al.
(författare)
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Rapid determination of acyclovir, its main metabolite 9-carboxymethoxymethylguanine, ganciclovir, and penciclovir in human serum using LC-MS/MS
- 2022
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Ingår i: BMC Biomedical chromotography. - Oxford, United Kingdom : John Wiley & Sons. - 0269-3879 .- 1099-0801. ; 36:4
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Tidskriftsartikel (refereegranskat)abstract
- A novel MS-based analytical method for simultaneous analysis of the antiviral drugs acyclovir, its metabolite 9-carboxymethoxymethylguanine, ganciclovir, and penciclovir in human serum is described. These antiviral drugs are active against herpes virus infections. Acyclovir and penciclovir are regarded as safe and effective medicines with mild side effects such as headache and gastrointestinal discomfort, and ganciclovir is regarded as more toxic and is known to cause, for example, bone marrow suppression. Acyclovirs main metabolite 9-carboxymethoxymethylguanine is a presumptive neurotoxin and should be monitored in patients with impaired renal function or in cases with neurotoxic symptoms. A sample was prepared using protein precipitation with 1% formic acid in methanol containing isotopically labeled internal standard. Chromatographic separation on a biphenyl column and mass spectrometric detection were performed in multiple reaction monitoring (MRM) mode on a Xevo TQ-S micro with ESI in positive ion mode, within 3 min. Inter-day assay accuracies for the quality controls varied between 95 and 104% and intra-day assay between 93 and 105%. Inter-day and intra-day assay imprecision for the quality controls ranged between 1.4 and 4.2% and 1.7 and 6.5% respectively. The lower limit of quantification for all four substances was 0.156 mu mol/L. It is an accurate and reproducible method for therapeutic drug monitoring.
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