Simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram in plasma using liquid chromatography-tandem mass spectrometry.

A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto-doxapram. The internal standard was fentanyl-d5 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity UPLC HSS T3 column with a run-time of only 5.0 min per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate or formic acid in Milli-Q ultrapure water or in methanol with a total flow rate of 0.4 mL min-1 . A plasma volume of only 50 µL was required to achieve adequate accuracy and precision. Calibration curves of all five analytes were linear. All analytes were stable for at least 48 h in the autosampler. The method was validated according to US Food and Drug Administration guidelines. This method allows quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram, which is useful for research as well as therapeutic drug monitoring, if applicable. The strength of this method is the combination of a small sample volume, a short run-time, a deuterated internal standard, an easy sample preparation method and the ability to simultaneously quantify all analytes in one run.

[Determination of methamphetamine in whole blood by capillary zone electrophoresis after solid phase extraction].

OBJECTIVE: To develop a specific CZE method for the determination of methamphetamine in whole blood after solid phase extraction. METHODS: With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood and the sample was analysized by CZE. RESULTS: The method showed excellent linearity and the linear correlation coefficient was 0.994. The relative standard deviation for between-day and within-day were 5.31% and 2.22%, respectively. CONCLUSION: The method is effective, simple, reliable and has been used in the determination of methamphetamine in whole blood.

A new look at the respiratory stimulant doxapram.

A number of life-threatening clinical disorders may be amenable to treatment with a drug that can stimulate respiratory drive. These include acute respiratory failure secondary to chronic obstructive pulmonary disease, post-anesthetic respiratory depression, and apnea of prematurity. Doxapram has been available for over forty years for the treatment of these conditions and it has a low side effect profile compared to other available agents. Generally though, the use of doxapram has been limited to these clinical niches involving patients in the intensive care, post-anesthesia care and neonatal intensive care units. Recent basic science studies have made considerable progress in understanding the molecular mechanism of doxapram's respiratory stimulant action. Although it is unlikely that doxapram will undergo a clinical renaissance based on this new understanding, it represents a significant advance in our knowledge of the control of breathing.

Determination of methamphetamine in whole blood by capillary zone electrophoresis after solid phase extraction / 法医学杂志

OBJECTIVE@#To develop a specific CZE method for the determination of methamphetamine in whole blood after solid phase extraction.@*METHODS@#With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood and the sample was analysized by CZE.@*RESULTS@#The method showed excellent linearity and the linear correlation coefficient was 0.994. The relative standard deviation for between-day and within-day were 5.31% and 2.22%, respectively.@*CONCLUSION@#The method is effective, simple, reliable and has been used in the determination of methamphetamine in whole blood.

Urinary metabolites of doxapram in premature neonates.

1. Urine samples from 20 premature neonates who received doxapram by i.v. infusion were analysed for drug metabolites by g.l.c-mass spectrometry. 2. In addition to doxapram, all urines contained at least one metabolite, but the known metabolite, 3-ketodoxapram, was detected in only 50% of the samples, and in some instances only in trace amounts. 3. Significant inter-individual differences in the metabolic pathways of doxapram were observed. 4. A total of six metabolites of doxapram were isolated three of which have not been observed previously in human or in dog. 5. Appropriate structures for the new metabolites have been deduced from their mass spectral fragmentation pathways, and are 1-ethyl-4-[2-(N-formyl-N-(2-hydroxy-ethyl)amino)ethyl]-3,3-diphenyl-2- pyrrolidinone (VII), 1-ethyl-4-[2-(4-morpholin-2-onyl)ethyl]-3,3-diphenyl-2-pyrro lidinone (IX) and 4-ethenyl-1-ethyl-3,3-diphenyl-2-pyrrolidinone (X).