Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Instrumentation
2.3. Working Solutions, Calibration Curve and Sample Preparation
2.4. Validation
3. Results
3.1. Optimization of Mass Spectrometry Parameters
3.2. Validation Results
3.3. Method Application and Toxicological Findings
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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No. | Substance | Ionization /Ion | Precursor Ion [m/z] | Product Ion [m/z] | Dwell Time (msec) | Q1 Pre-Bias [V] | Collision Energy [V] | Q3 Pre-Bias [V] | Retention Time [min] |
---|---|---|---|---|---|---|---|---|---|
1 | Carboprost | Negative [M−H]− | 367.3 | 323.3 * | 1 | 19 | 21 | 12 | 5.914 |
171.15 | 1 | 27 | 26 | 12 | |||||
209.2 | 1 | 14 | 23 | 14 | |||||
165.15 | 1 | 14 | 26 | 11 | |||||
261.2 | 1 | 27 | 25 | 17 | |||||
2 | Cloprostenol | Negative [M−H]− | 423.0 | 127.05 * | 1 | 13 | 27 | 23 | 5.775 |
295.2 | 1 | 22 | 18 | 21 | |||||
259.2 | 1 | 23 | 17 | 18 | |||||
233.2 | 1 | 16 | 21 | 16 | |||||
189.15 | 1 | 16 | 24 | 13 | |||||
3 | Dinoprost (PGF2α) | Negative [M−H]− | 353.1 | 309.3 | 1 | 26 | 19 | 11 | 5.791 |
193.25 * | 1 | 26 | 25 | 13 | |||||
291.3 | 1 | 26 | 22 | 21 | |||||
247.3 | 1 | 26 | 23 | 17 | |||||
335.4 | 1 | 26 | 17 | 12 | |||||
4 | Dinoprostone (PGE2) | Negative [M−H]− | 351.1 | 271.25 * | 1 | 18 | 17 | 13 | 5.719 |
315.25 | 1 | 26 | 13 | 11 | |||||
333.3 | 1 | 25 | 13 | 12 | |||||
189.15 | 1 | 25 | 20 | 13 | |||||
233.15 | 1 | 18 | 13 | 17 | |||||
5 | Misoprostol | Positive [M+Na]+ | 405.0 | 23.1 * | 1 | −19 | −55 | −26 | 6.237 |
305.25 | 1 | −23 | −22 | −14 | |||||
387.2 | 1 | −25 | −25 | −13 | |||||
6 | Sulprostone | Negative [M−H]− | 464.0 | 446.35 | 1 | 11 | 20 | 16 | 4.951 |
334.3 | 1 | 24 | 23 | 12 | |||||
310.2 | 1 | 25 | 25 | 22 | |||||
94.05 * | 1 | 18 | 29 | 16 | |||||
93.1 | 1 | 14 | 41 | 15 | |||||
IS1 | Dinoprost-d4 (PGF2α-d4) | Negative [M−H]− | 357.3 | 313.3 * | 1 | 20 | 19 | 11 | 5.785 |
197.25 | 1 | 19 | 25 | 14 | |||||
295.4 | 1 | 19 | 22 | 21 | |||||
251.3 | 1 | 19 | 23 | 16 | |||||
213.3 | 1 | 19 | 17 | 15 | |||||
IS2 | Misoprostol-d5 | Positive [M+Na]+ | 410.0 | 23.0 * | 1 | −22 | −55 | −26 | 6.232 |
305.2 | 1 | −19 | −22 | −21 | |||||
392.3 | 1 | −20 | −24 | −26 |
Calibration Curve | Validation Results | ||||||
---|---|---|---|---|---|---|---|
Substance | Internal Standard | The Coefficient of Determination (R2) | Concentration Level [µg/mL] | Intraday | Interday | ||
Precision [%] * | Accuracy [%] * | Precision [%] * | Accuracy [%] * | ||||
Carboprost | Dinoprost-d4 (PG-F2α-d4) | >0.9988 | 0.1 1 10 | 2.9 2.4 3.3 | −4.5 −3.8 1.4 | 3.0 4.4 1.2 | 0.3 −0.2 −0.6 |
Cloprostenol | Dinoprost-d4 (PG-F2α-d4) | >0.9988 | 0.1 1 10 | 2.4 1.5 2.4 | 4.3 −4.1 1.8 | 2.5 1.0 1.1 | 4.0 −3.8 1.0 |
Dinoprost (PG-F2α) | Dinoprost-d4 (PG-F2α-d4) | >0.9980 | 0.1 1 10 | 5.0 4.2 1.4 | 3.0 −0.9 3.6 | 3.8 4.7 2.4 | 5.0 2.6 3.0 |
Dinoprostone (PG-E2) | Dinoprost-d4 (PG-F2α-d4) | >0.9977 | 0.1 1 10 | 4.4 3.5 1.8 | 4.3 −3.1 4.3 | 2.4 0.8 0.7 | 4.7 −0.9 3.0 |
Misoprostol | Misoprostol-d5 | >0.9991 | 0.1 1 10 | 1.0 4.2 2.2 | 5.0 2.1 4.8 | 4.2 2.2 1.6 | 4.0 −1.2 3.1 |
Sulprostone | Dinoprost-d4 (PG-F2α-d4) | >0.9988 | 0.1 1 10 | 1.9 4.1 4.9 | 5.0 2.7 −3.4 | 3.5 4.5 2.9 | 4.0 2.0 −1.4 |
Method | Prostaglandins | Details of the Method | Tested Samples | Qualitative/ Quantitative | Year | Reference |
---|---|---|---|---|---|---|
ATR-FTIR | Misoprostol | Characteristic wavelengths: 3304, 1737, 1364, 1016 cm−1 | Pills | Qualitative | 2022 | [14] |
Spectrophotometry | Misoprostol | Absorbance measured at 247.6 nm | Pills | Quantitative | 2011 | [15] |
HPLC-UV | Carboprost | Chromatographic column: Symmetry C18 (100 × 4.6 mm × 3.5 µm); Absorbance measured at 200 nm; | Injection liquids | Quantitative | 2014 | [16] |
LC-MS | Misoprostol | Comparison of chromatograms obtained during analysis of authentic samples with chromatograms obtained for Cytotec® tablets (reference material) | Abortion pills collected from vagina during gynecological examination | Qualitative | 2019 | [24] |
LC-QTOF-MS/MS | Carboprost Misoprostol | Chromatographic column: Suplex™PKB (250 × 2.1 mm × 5 µm); Mass spectrometry: ESI (sodium adducts in positive ionization); MRM | Infusion preparations | Quantitative | 2007 | [18] |
LC-QTRAP-MS/MS | Misoprostol | Chromatographic column: Capcell PAK C18 MGII (50 × 2.0 mm × 3 µm); Mass spectrometry: ESI (negative ionization); MRM | Counterfeit drugs distributed in the illegal marketplaces | Quantitative | 2019 | [17] |
UHPLC-QqQ-MS/MS | Carboprost Cloprostenol Dinoprost (PG-F2α) Dinoprstone (PG-E2) Misoprostol Sulprostone | Chromatographic column: Acquity UPLC BEH C18 (50 × 2.1 mm × 1.7 µm); Mass spectrometry: ESI (sodium adducts in positive ionization & negative ionization); MRM | Abortion pills collected from vagina during gynecological examination | Quantitative | 2022 | Presented method |
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Szpot, P.; Wachełko, O.; Zawadzki, M. Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations. Toxics 2023, 11, 802. https://doi.org/10.3390/toxics11100802
Szpot P, Wachełko O, Zawadzki M. Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations. Toxics. 2023; 11(10):802. https://doi.org/10.3390/toxics11100802
Chicago/Turabian StyleSzpot, Paweł, Olga Wachełko, and Marcin Zawadzki. 2023. "Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations" Toxics 11, no. 10: 802. https://doi.org/10.3390/toxics11100802