Analysis of caffeine and paraxanthine in human saliva with ultra-high-performance liquid chromatography for CYP1A2 phenotyping

Jordan, Nan Yeun; Mimpen, Jolet Y; Bogaard, Willie J. M. van den; Flesch, Frits M.; Meent, Michiel H.M. van de; Toraño, Javier Sastre

doi:10.1016/j.jchromb.2015.05.020

Cited by 13 publications

(9 citation statements)

References 15 publications

(5 reference statements)

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“…In humans, caffeine is metabolized through the liver microsomal drug-metabolizing enzyme system CYP450. In neonates, the expression of this enzymatic system is dependent on their prenatal and postnatal age [ 10 , 12 ]. It has been suggested that the therapeutic effects of caffeine are affected by the expression and type of CYP1A2 isoform present (main metabolic pathway), which affects not only plasma concentration of caffeine (Caf) and its metabolites (theophylline (Theo), theobromine (Theb), and paraxanthine (Par)) ( Figure 1 ) but also its therapeutic effects [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure

López-Sánchez

Díaz

Aranda-Gutierrez

et al. 2018

Journal of Analytical Methods in Chemistry

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Caffeine is recognized as the first-line therapeutic agent for apnea of prematurity. The dosage regimen is 10 mg/kg loading dose and 2.5 mg/kg maintenance dose. However, the plasma concentration achieved, not always, is therapeutically useful. It makes necessary to increase the doses to reach plasma concentration up to 30 or 35 μg/mL or even higher to attain therapeutic effect. To study why neonates have these differences, and whether these effects are linked to prenatal caffeine exposure, we had to develop an analytical method for an accurate measurement of caffeine and metabolites concentration. The analysis was carried out using fetal bovine serum (FBS) as biological matrix in a high-performance liquid chromatography with an ultraviolet detector method. This method allows acceptable chromatographic resolution between analytes in 15 minutes. It was validated and proved to be linear in the 0.1–40 µg/mL range for caffeine, paraxanthine, theobromine, and theophylline in the same chromatographic analysis. Accuracy for quality control samples for intra- and interday assays was ranged from 96.5 to 105.2% and 97.1 to 106.2%. Precision had CV no more than 10% in all concentration levels for all analytes. No differences were observed between quantification in human and FBS. This method was applied to quantify plasma drug concentration in mothers and their newborns in a Mexican northeast population. In our study, we confirmed self-reported caffeine maternal intake in 85.2% (n=23); meanwhile, in their newborn's plasma, it was detected only in 78% (n=21). Caffeine plasma concentrations in mother and newborn had a linear relationship, and no differences were observed between groups (mothers versus children). These results suggest that our analytical method and substitution of biological matrix was linear, precise, and accurate for caffeine quantification and could be used for measuring prenatal exposure and let us to study, in the future, concentration differences observed during apnea clinical treatment.

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Section: Introductionmentioning

confidence: 99%

HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure

López-Sánchez

Díaz

Aranda-Gutierrez

et al. 2018

Journal of Analytical Methods in Chemistry

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“…With the gain of scientific knowledge and the advances in analytical technologies, significant improvements in the cocktail approach have been observed in recent years. The authors of some of the recent cocktails have concentrated their efforts in developing phenotyping strategies using low probe dose whereas others worked more on the aspects of alternative, less‐invasive sampling methods .…”

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confidence: 99%

Evaluation of Mutual Drug–Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method

Bosilkovska

Samer

Déglon

et al. 2016

Basic Clin Pharma Tox

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Cytochrome P450 (CYP) activity can be assessed using a 'cocktail' phenotyping approach. Recently, we have developed a cocktail (Geneva cocktail) which combines the use of low-dose probes with a low-invasiveness dried blood spots (DBS) sampling technique and a single analytical method for the phenotyping of six major CYP isoforms. We have previously demonstrated that modulation of CYP activity after pre-treatment with CYP inhibitors/inducer could be reliably predicted using Geneva cocktail. To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions. In a randomized, four-way, Latin-square crossover study, 30 healthy volunteers received low-dose caffeine, flurbiprofen, omeprazole, dextromethorphan and midazolam (a previously validated combination with no mutual drug-drug interactions); fexofenadine alone; bupropion alone; or all seven drugs simultaneously (Geneva cocktail). Pharmacokinetic profiles of the probe drugs and their metabolites were determined in DBS samples using both conventional micropipette sampling and new microfluidic device allowing for self-sampling. The 90% confidence intervals for the geometric mean ratios of AUC metabolite/AUC probe for CYP probes administered alone or within Geneva cocktail fell within the 0.8-1.25 bioequivalence range indicating the absence of pharmacokinetic interaction. The same result was observed for the chosen phenotyping indices, that is metabolic ratios at 2 hr (CYP1A2, CYP3A) or 3 hr (CYP2B6, CYP2C9, CYP2C19, CYP2D6) post-cocktail administration. DBS sampling could successfully be performed using a new microfluidic device. In conclusion, Geneva cocktail combined with an innovative DBS sampling device can be used routinely as a test for simultaneous CYP phenotyping.

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“…Some reports have proposed that molar concentration ratios of CA and its primary or secondary metabolites, such as PX/CA, TB/CA and (TP + TB + PX)/CA, in plasma, urinary or saliva, could be potentially useful to investigate the variation of CYP1A2 activity under the effects of non‐genetic and genetic polymorphism factors in adults who consumed CA‐content beverages (Caubet et al, 2004; Jodynis‐Liebert et al, 2004; Jordan et al, 2015; Klein et al, 2010; Murayama et al, 2016; Sinues et al, 1999; Tian et al, 2019; Urry et al, 2016; Yim et al, 2013). Evaluating the change characteristics of enzyme activity through variations in the ratios of metabolites might be an alternative method to predict drug reaction for medication safety in premature infants.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, both failed to quantify these four analytes simultaneously using 100 μL plasma because of the low sensitivity of the HPLC method. Several quantitative methods for determination of CA and its different metabolites in plasma, urine and saliva in adult volunteers have been reported, for example, HPLC, micellar electrokinetic capillary chromatography and MS (Begas et al, 2015; Caubet et al, 2002; Dobson et al, 2016; Han et al, 2020; Jordan et al, 2015; Ptolemy et al, 2010; Turjap et al, 2016). An HPLC–tandem mass spectrometry (MS/MS) method has been reported to quantify CA, PX, TP and TB simultaneously in human plasma with the linear range of CA from 4.1 to 3000 ng/mL (Chen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantitation of serum caffeine and its metabolites by ultra‐high‐performance liquid chromatography–tandem mass spectrometry for CYP1A2 activity prediction in premature infants

Jiang

Gao

Liang

et al. 2021

Biomedical Chromatography

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Caffeine (CA) is accepted as a probe of cytochrome P450 1A2 enzyme (CYP1A2) activity and is commonly used in premature infants with great inter‐individual variability of metabolism. To evaluate the change characteristics of CYP1A2 activity in premature infants, an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method was developed and optimized for the simultaneous quantitation of serum CA and its major metabolites, including paraxanthine (PX), theophylline (TP) and theobromine (TB), in premature infants. A C18 column and gradient elution with 0.1% formic acid in methanol and 0.1% formic acid in water at a flow rate of 0.3 mL/min were used for compound separation. The mass spectrometer monitored the transitions of CA (m/z 195.0 → 138.0), CA‐d9 (m/z 204.0 → 144.1), PX (m/z 181.0 → 124.1), TP (m/z 181.0 → 123.9) and TB (m/z 181.0 → 138.0) using multiple reaction monitoring in positive ion mode. CYP1A2 activity was evaluated by serum molar concentration ratios of CA and its metabolites. The results showed that CYP1A2 has a significant positive correlation with the clearance of CA, and was affected by current weight and CYP1A2*1C. The results suggested that the serum concentration ratios of CA metabolites could be used to predict the changes in CYP1A2 enzyme activity in premature infants.

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Analysis of caffeine and paraxanthine in human saliva with ultra-high-performance liquid chromatography for CYP1A2 phenotyping

Cited by 13 publications

References 15 publications

HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure

HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure

Evaluation of Mutual Drug–Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method

Simultaneous quantitation of serum caffeine and its metabolites by ultra‐high‐performance liquid chromatography–tandem mass spectrometry for CYP1A2 activity prediction in premature infants

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